MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of Autoimmunity' source. Wed, 08 Feb 2012 06:42:56 +0100 http://www.medworm.com/index.php?rid=5625211&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264504%26dopt%3DAbstract Authors: Barzaghi F, Passerini L, Gambineri E, Ciullini Mannurita S, Cornu T, Kang ES, Choe YH, Cancrini C, Corrente S, Ciccocioppo R, Cecconi M, Zuin G, Discepolo V, Sartirana C, Schmidtko J, Ikinciogullari A, Ambrosi A, Roncarolo MG, Olek S, Bacchetta R Abstract Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked (IPEX) syndrome is a unique example of primary immunodeficiency characterized by autoimmune manifestations due to defective regulatory T (Treg) cells, in the presence of FOXP3 mutations. However, autoimmune symptoms phenotypically resembling IPEX often occur in the absence of detectable FOXP3 mutations. The cause of this "IPEX-like" syndrome presently remains unclear. To investigate whether a defect in Treg cells sustains the immunological dysregulation in IPE... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5625211 Wed, 18 Jan 2012 05:00:00 +0100 5625211 http://www.medworm.com/index.php?rid=5625213&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261500%26dopt%3DAbstract Authors: Lateef A, Petri M Abstract Sex hormones, including estrogens, influence the immune system in a complex manner, playing an important role in the pathophysiology of autoimmune diseases. Estrogen receptors can be found in almost all cells, including those of the adaptive and innate immune systems. Depending on the relative preponderance and stimulation of different receptors in various tissues, estrogens may demonstrate pro-inflammatory or anti-inflammatory properties. Traditionally, exogenous estrogens were considered to have the potential of worsening the autoimmune processes and hence were avoided in patients with rheumatic diseases. Recent studies have demonstrated the efficacy of exogenous hormone therapies, either in the form of oral contraceptives or post-menopausal ho... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5625213 Tue, 17 Jan 2012 05:00:00 +0100 5625213 http://www.medworm.com/index.php?rid=5625212&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261501%26dopt%3DAbstract CONCLUSIONS: This study demonstrates that poor disease control in the year prior to pregnancy and the absence of drug therapy are associated with poor outcomes whist pregnant. These data should facilitate appropriate pre-conception counselling and appropriate pregnancy management in this cohort. PMID: 22261501 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5625212 Tue, 17 Jan 2012 05:00:00 +0100 5625212 http://www.medworm.com/index.php?rid=5625214&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257939%26dopt%3DAbstract Authors: Tischner D, Gaggl I, Peschel I, Kaufmann M, Tuzlak S, Drach M, Thuille N, Villunger A, Jan Wiegers G Abstract The Bcl-2 regulated apoptosis pathway is critical for the elimination of autoreactive lymphocytes, thereby precluding autoimmunity. T cells escaping this process can be kept in check by regulatory T (Treg) cells expressing the transcription and lineage commitment factor Foxp3. Despite the well-established role of Bcl-2 family proteins in shaping the immune system and their frequent deregulation in autoimmune pathologies, it is poorly understood how these proteins affect Treg cell development and function. Here we compared the relative expression of a panel of 40 apoptosis-associated genes in Treg vs. conventional CD4(+) T cells. Physiological significance of key-ch... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5625214 Mon, 16 Jan 2012 05:00:00 +0100 5625214 http://www.medworm.com/index.php?rid=5579140&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226784%26dopt%3DAbstract This study assessed the association between such pregnancy-related experiences and the subsequent risk of female predominant and other ADs. Our study cohort comprised 1.6 million Danish women born since 1955 for whom we had information about hyperemesis, gestational hypertensive disorders and pregnancy losses and subsequent hospital contacts for 31 ADs between 1982 and 2008. Ratios of first hospitalization rates (RRs) with 95% confidence intervals (CIs) were calculated using Poisson regression, adjusting for age, birth cohort, calendar period, marital status and childbirths. During 27.0 million person-years of follow-up 51,732 women were hospitalized with one or more ADs. Overall, compared with women without the specific pregnancy experiences, the risk of any AD was significantly increased... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5579140 Thu, 05 Jan 2012 05:00:00 +0100 5579140 http://www.medworm.com/index.php?rid=5579142&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225601%26dopt%3DAbstract Authors: Pennell LM, Galligan CL, Fish EN Abstract Sex based differences in immune responses, affecting both the innate and adaptive immune responses, contribute to differences in the pathogenesis of infectious diseases in males and females, the response to viral vaccines and the prevalence of autoimmune diseases [1-5]. Indeed, females have a lower burden of bacterial, viral and parasitic infections, most evident during their reproductive years [2,6]. Conversely, females have a higher prevalence of a number of autoimmune diseases, including Sjogren's syndrome, systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis (RA) and multiple sclerosis (MS). These observations suggest that gonadal hormones may have a role in this sex differential. The fundamental differences in... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5579142 Wed, 04 Jan 2012 05:00:00 +0100 5579142 http://www.medworm.com/index.php?rid=5579141&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225602%26dopt%3DAbstract Authors: Tian L, De Hertogh G, Fedeli M, Staats KA, Schonefeldt S, Humblet-Baron S, Van Den Bosch L, Dellabona P, Dooley J, Liston A Abstract With an increasing number of studies demonstrating alterations in T cell microRNA expression during autoimmune disease, modulation of the T cell microRNA network is considered a potential therapeutic strategy. Due to the complex and often opposing interactions of individual microRNA, prioritization of therapeutic targets first requires dissecting the dominant effects of the T cell microRNA network. Initial results utilizing a unidirectional screen suggested that the tolerogenic functions were dominant, with spontaneous colitis resulting from T cell-specific excision of Dicer. Here we performed a bidirectional screen for microRNA function by r... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5579141 Wed, 04 Jan 2012 05:00:00 +0100 5579141 http://www.medworm.com/index.php?rid=5579144&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22218218%26dopt%3DAbstract Authors: Twig G, Shina A, Amital H, Shoenfeld Y Abstract Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 4% of women during the age of fertility. A growing body of clinical studies links thyroid autoimmunity as a cause of infertility and adverse pregnancy outcomes that includes miscarriage or preterm deliveries. Importantly, these adverse effects are persistent in euthyroid women. In the current review we elaborate on the pathogenesis that underlies infertility and increased pregnancy loss among women with autoimmune thyroid disease. Such mechanisms include thyroid autoantibodies that exert their effect in a TSH-dependent but also in a TSH-independent manner. The later includes quantitative and qualitative changes in the profile of endometrial T cells... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5579144 Tue, 03 Jan 2012 05:00:00 +0100 5579144 http://www.medworm.com/index.php?rid=5579143&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222237%26dopt%3DAbstract Authors: Shoenfeld Y, Tincani A, Gershwin ME Abstract The 7th International Congress of Autoimmunity was held in Ljubljana, Slovenia in May 2010. At the conclusion of the Congress, a list was prepared of the major unresolved clinical issues in autoimmunity. The list grew to be extensive but one subject that was found in nearly all of the concerns was geoepidemiology of autoimmunity and, in particular, the increased risk of women to develop autoimmune disease. Indeed, one does not need to be an autoimmunologist to appreciate that the risk of developing rheumatoid arthritis, for example, has been known to be increased in women compared to men, almost from the time of its original description. In fact, although the sex ratios of autoimmune disease have varied from center to center, fr... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5579143 Tue, 03 Jan 2012 05:00:00 +0100 5579143 http://www.medworm.com/index.php?rid=5563046&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209352%26dopt%3DAbstract Authors: Baldini C, Talarico R, Tzioufas AG, Bombardieri S Abstract Over the years, several different criteria sets have been proposed for the classification of Sjögren's syndrome (SS), but none of them has been widely adopted by the scientific community until the publication of the 1993 Preliminary European Classification criteria. These Classification criteria have been largely employed both in clinical practice and in observational and interventional studies for many years. In 2002 the Preliminary European Criteria were re-examined by a joint American and European Committee. The result of this revision were the American and European Consensus Group classification criteria (AECG-criteria) which introduced more clearly defined rules for classifying patients with primary or second... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5563046 Fri, 30 Dec 2011 05:00:00 +0100 5563046 http://www.medworm.com/index.php?rid=5563047&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209097%26dopt%3DAbstract Authors: Geurs TL, Hill EB, Lippold DM, French AR Abstract Increased susceptibility to autoimmunity in females is often viewed as the consequence of enhanced immunoreactivity providing superior protection against infections. We paradoxically observed greater mortality in female compared to male mice during systemic viral infections with three large double-stranded DNA viruses (herpes simplex virus type I [HSV], murine cytomegalovirus [MCMV], and vaccinia virus [VV]). Indeed, female mice were 27-fold more susceptible to infection with HSV than male mice. Elimination of estrogen by ovariectomy in female mice or addition of estrogen to castrated male mice only partially eliminated the observed sex differences following HSV infection. However, the differences observed in survival betwe... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5563047 Thu, 29 Dec 2011 05:00:00 +0100 5563047 http://www.medworm.com/index.php?rid=5551686&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204899%26dopt%3DAbstract Authors: Andreoli L, Fredi M, Nalli C, Reggia R, Lojacono A, Motta M, Tincani A Abstract Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: "safe" drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxi... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5551686 Mon, 26 Dec 2011 05:00:00 +0100 5551686 http://www.medworm.com/index.php?rid=5551685&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204900%26dopt%3DAbstract Authors: Amur S, Parekh A, Mummaneni P Abstract Autoimmune diseases (AIDs) are believed to be multifactorial diseases that commonly involve multiple organ systems. About three fourth of the patients afflicted with AIDs are women suggesting that sex differences impact the incidence of AID. However, the proportion of females to males suffering from AID varies depending on the disease. The response to some AID therapeutics also differs in females versus males, suggesting that enrollment of adequate numbers of women and men is important in clinical trials for development of AID drugs. It is known for a long time that genetic factors are important contributors to AID susceptibility. Currently available information suggests that multiple genes with modest association to AID contribute to... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5551685 Mon, 26 Dec 2011 05:00:00 +0100 5551685 http://www.medworm.com/index.php?rid=5551687&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197557%26dopt%3DAbstract We report that following co-culture with autologous CD4+CD25- responder T cells, human CD14+ monocytes and monocyte-derived macrophages become activated but also significantly more prone to apoptosis than monocytes/macrophages cultured alone. In contrast, in the presence of CD4+CD25+ regulatory T cells (Tregs), monocytes and macrophages survive whilst adopting an anti-inflammatory phenotype. The induction of monocyte death requires responder T cell activation and cell-contact between responder T cells and monocytes. We demonstrate a critical role for FAS/FAS-L ligation in responder T cell-induced monocyte killing since responder T cells, but not Tregs, upregulate FAS-ligand (FAS-L) mRNA, and induce FAS expression on monocytes. Furthermore, responder T cell-induced monocyte apoptosis is blo... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5551687 Fri, 23 Dec 2011 05:00:00 +0100 5551687 http://www.medworm.com/index.php?rid=5551689&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22196921%26dopt%3DAbstract Authors: Persani L, Bonomi M, Lleo A, Pasini S, Civardi F, Bianchi I, Campi I, Finelli P, Miozzo M, Castronovo C, Sirchia S, Gershwin ME, Invernizzi P Abstract Multiple mechanisms have been proposed to explain the peculiar distribution of autoimmune thyroiditis (AIT) among women and men. Most attention has been focused on the detection of the role of estrogens and the X chromosome. Specifically, a potential role for X haploinsufficiency has been proposed in the female patient population and an association with the disease has been confirmed. Our knowledge of the etiopathogenesis of autoimmunity in male patients remains, however, limited. Next to the possible role of androgens and their imbalances, the Y chromosome appears as a potential candidate for influence of the immune functio... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5551689 Thu, 22 Dec 2011 05:00:00 +0100 5551689 http://www.medworm.com/index.php?rid=5551688&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22196923%26dopt%3DAbstract Authors: Martinez de la Torre Y, Pregnolato F, D'Amelio F, Grossi C, Disimone N, Pasqualini F, Nebuloni M, Chen P, Pierangeli S, Bassani N, Ambrogi F, Borghi MO, Vecchi A, Locati M, Meroni PL Abstract β2 glycoprotein I (β2GPI)-dependent anti-phospholipid antibodies (aPL) induce thrombosis and affect pregnancy. The CMV-derived synthetic peptide TIFI mimics the PL-binding site of β2GPI and inhibits β2GPI cell-binding in vitro and aPL-mediated thrombosis in vivo. Here we investigated the effect of TIFI on aPL-induced fetal loss in mice. TIFI inhibitory effect on in vitro aPL binding to human trophoblasts was evaluated by indirect immunofluorescence and ELISA. TIFI effect on aPL-induced fetal loss was investigated in pregnant C57BL/6 mice treated with aPL or normal IgG (NHS). Pl... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5551688 Thu, 22 Dec 2011 05:00:00 +0100 5551688 http://www.medworm.com/index.php?rid=5536971&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22186068%26dopt%3DAbstract We examined whether IL-12 treatment prevented diabetes by injecting different doses of IL-12 into NOD mice and compared the incidence of diabetes and insulitis in NOD mice with the incidence in control mice. Furthermore, we investigated the potential mechanisms of IL-12-mediated prevention of diabetes and insulitis. The expression of pro-inflammatory and immunoregulatory cytokines was measured before and following therapeutic administration of IL-12 in NOD mice. Our data demonstrated that both the absolute number and the function of DCs were impaired in NOD mice and that the levels of the Th17-associated pro-inflammatory cytokines, IL-1β, IL-6 and IL-23, were elevated in NOD mice compared with age-matched BALB/c and C57BL/6 mice. However, treatment of NOD mice with IL-12 suppressed insuli... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536971 Sun, 18 Dec 2011 05:00:00 +0100 5536971 http://www.medworm.com/index.php?rid=5536973&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178198%26dopt%3DAbstract Authors: Bianchi I, Lleo A, Gershwin ME, Invernizzi P Abstract The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. A... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536973 Thu, 15 Dec 2011 05:00:00 +0100 5536973 http://www.medworm.com/index.php?rid=5536972&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178199%26dopt%3DAbstract Authors: Selmi C, Meroni PL, Gershwin ME Abstract Primary biliary cirrhosis (PBC) has been often coined a model autoimmune disease based on the homogeneity amongst patients, the frequency and similarity of antimitochondrial antibodies, including the highly directed immune response to pyruvate dehydrogenase (PDC-E2). A significant number of patients with PBC suffer from sicca and amongst these, there are patients who also have classic Sjögren's syndrome. Indeed, both PBC and Sjögren's syndrome are characterized by inflammation of target epithelial elements. Both diseases can be considered on the basis of a number of other related clinical aspects, including proposed unique apoptotic features of the target tissue, the role of secretory IgA, and the frequency with which both disease... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536972 Thu, 15 Dec 2011 05:00:00 +0100 5536972 http://www.medworm.com/index.php?rid=5536974&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177232%26dopt%3DAbstract Authors: Bogdanos DP, Smyk DS, Rigopoulou EI, Mytilinaiou MG, Heneghan MA, Selmi C, Eric Gershwin M Abstract Twin studies are powerful tools to discriminate whether a complex disease is due to genetic or environmental factors. High concordance rates among monozygotic (MZ) twins support genetic factors being predominantly involved, whilst low rates are suggestive of environmental factors. Twin studies have often been utilised in the study of systemic and organ specific autoimmune diseases. As an example, type I diabetes mellitus has been investigated to establish that that disease is largely affected by genetic factors, compared to rheumatoid arthritis or scleroderma, which have a weaker genetic association. However, large twin studies are scarce or virtually non-existent in other a... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536974 Wed, 14 Dec 2011 05:00:00 +0100 5536974 http://www.medworm.com/index.php?rid=5536975&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154464%26dopt%3DAbstract Authors: Yan Y, Wang YH, Diamond B Abstract The generation of a B cell repertoire involves producing and subsequently purging autoreactive B cells. Receptor editing, clonal deletion and anergy are key mechanisms of central B cell tolerance. Somatic mutation of antigen-activated B cells within the germinal center produces a second wave of autoreactivity; but the regulatory mechanisms that operate at this phase of B cell activation are poorly understood. We recently identified a post germinal center tolerance checkpoint, where receptor editing is re-induced to extinguish autoreactivity that is generated by somatic hypermutation. Re-induction of the recombinase genes RAG1 and RAG2 in antigen-activated B cells requires antigen to engage the B cell receptor and IL-7 to signal through th... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536975 Wed, 07 Dec 2011 05:00:00 +0100 5536975 http://www.medworm.com/index.php?rid=5536976&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154021%26dopt%3DAbstract Authors: Dillon SP, Kurien BT, Li S, Bruner GR, Kaufman KM, Harley JB, Gaffney PM, Wallace DJ, Weisman MH, Scofield RH Abstract About 90% of patients with systemic lupus erythematosus (SLE) are female. We hypothesize that the number of X chromosomes, not sex, is a determinate of risk of SLE. Number of X chromosomes was determined by single nucleotide typing and then confirmed by karyotype or fluorescent in situ hybridization in a large group of men with SLE. Presence of an sry gene was assessed by RT-PCR. We calculated 96% confidence intervals using the Adjusted Wald method, and used Bayes' theorem to estimate the prevalence of SLE among 47,XXY and 46,XX men. Among 316 men with SLE, 7 had 47,XXY and 1 had 46,XX. The rate of Klinefelter's syndrome (47,XXY) was statistically differen... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536976 Mon, 05 Dec 2011 05:00:00 +0100 5536976 http://www.medworm.com/index.php?rid=5536977&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142890%26dopt%3DAbstract Authors: Strickland FM, Hewagama A, Lu Q, Wu A, Hinderer R, Webb R, Johnson K, Sawalha AH, Delaney C, Yung R, Richardson BC Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used (C57BL/6xSJL)F1 mice transgenic for a dominant-negative MEK (dnMEK) that was previously shown to be inducibly and selectively expressed in T cells. In this model, induction of the dnMEK by doxycycline treatment suppresses T cell ERK signaling, decreasing DNA-methyltransferase expression and resulting in DNA deme... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536977 Sat, 03 Dec 2011 05:00:00 +0100 5536977 http://www.medworm.com/index.php?rid=5536978&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137891%26dopt%3DAbstract Authors: Pollard KM Abstract Autoimmunity is thought to result from a combination of genetics, environmental triggers, and stochastic events. Gender is also a significant risk factor with many diseases exhibiting a female bias. Although the role of environmental triggers, especially medications, in eliciting autoimmunity is well established less is known about the interplay between gender, the environment and autoimmunity. This review examines the contribution of gender in autoimmunity induced by selected chemical, physical and biological agents in humans and animal models. Epidemiological studies reveal that environmental factors can be associated with a gender bias in human autoimmunity. However many studies show that the increased risk of autoimmunity is often influenced by occu... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536978 Fri, 02 Dec 2011 05:00:00 +0100 5536978 http://www.medworm.com/index.php?rid=5536979&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22123179%26dopt%3DAbstract In this study, we investigate the potential contribution of these cells to disease processes in a subgroup of multiple sclerosis (MS) and rheumatoid arthritis (RA) patients. Characterization of CD4(+)CD28(-) T cells in patients and healthy controls reveals that they have an inflammation-seeking effector-memory T cell phenotype with cytotoxic properties, as they expel cytotoxic granules in response to a polyclonal stimulus or MS-related autoantigens. We identify CX(3)CR1, the fractalkine receptor, as a selective marker to discriminate CD4(+)CD28(-) T cells from their CD4(+)CD28(+) counterparts. CX(3)CR1 expression enables CD4(+)CD28(-) T cells to migrate towards a fractalkine gradient in vitro. In addition, we find increased levels of fractalkine in the cerebrospinal fluid and inflammatory... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536979 Sat, 26 Nov 2011 05:00:00 +0100 5536979 http://www.medworm.com/index.php?rid=5536980&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22119415%26dopt%3DAbstract In conclusion, we propose gender-based systems biology as a novel tool to gain fundamental information on disease-associated functional processes. PMID: 22119415 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5536980 Thu, 24 Nov 2011 05:00:00 +0100 5536980 http://www.medworm.com/index.php?rid=5424202&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079680%26dopt%3DAbstract Authors: Quintero OL, Amador-Patarroyo MJ, Montoya-Ortiz G, Rojas-Villarraga A, Anaya JM Abstract A large number of autoimmune diseases (ADs) are more prevalent in women. The more frequent the AD and the later it appears, the more women are affected. Many ideas mainly based on hormonal and genetic factors that influence the autoimmune systems of females and males differently, have been proposed to explain this predominance. These hypotheses have gained credence mostly because many of these diseases appear or fluctuate when there are hormonal changes such as in late adolescence and pregnancy. Differences in X chromosome characteristics between men and women with an AD have led researchers to think that the genetic background of this group of diseases also relates to the genetic dete... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5424202 Fri, 11 Nov 2011 05:00:00 +0100 5424202 http://www.medworm.com/index.php?rid=5424203&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22063316%26dopt%3DAbstract Authors: Bresson D, Fousteri G, Manenkova Y, Croft M, von Herrath M Abstract Antigen-specific therapies are possibly the safest approach to prevent type 1 diabetes (T1D). However their clinical translation has yielded poor results and greater efforts need to be put into the development of novel strategies to ameliorate their clinical outcome. OX40 is a costimulatory molecule expressed by T cells after antigen recognition and has been implicated in the control effector but also regulatory T cells (Tregs) function in vivo. The activity of OX40 signal on Tregs function has been controversial. In this context we investigated whether an anti-OX40 agonist antibody treatment can ameliorate antigen-specific immune intervention for the prevention of T1D. We show that treatment of non-obese... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5424203 Sat, 05 Nov 2011 04:00:00 +0100 5424203 http://www.medworm.com/index.php?rid=5382199&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018711%26dopt%3DAbstract Authors: Huarte E, Rynda-Apple A, Riccardi C, Skyberg JA, Golden S, Rollins MF, Ramstead AG, Jackiw LO, Maddaloni M, Pascual DW Abstract Natural killer (NK) cells and dendritic cells (DCs) have been shown to link the innate and adaptive immune systems. Likewise, a new innate cell subset, interferon-producing killer DCs (IKDCs), shares phenotypic and functional characteristics with both DCs and NK cells. Here, we show IKDCs play an essential role in the resolution of experimental autoimmune encephalomyelitis (EAE) upon treatment with the tolerizing agent, myelin oligodendrocyte glycoprotein (MOG), genetically fused to reovirus protein σ1 (termed MOG-pσ1). Activated IKDCs were recruited subsequent MOG-pσ1 treatment of EAE, and disease resolution was abated upon NK1.1 cell depletio... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5382199 Fri, 21 Oct 2011 04:00:00 +0100 5382199 http://www.medworm.com/index.php?rid=5382200&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014533%26dopt%3DAbstract Authors: Zhang Q, Long H, Liao J, Zhao M, Liang G, Wu X, Zhang P, Ding S, Luo S, Lu Q Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T cell overactivation and B cell hyper-stimulation. Hematopoietic progenitor kinase 1 (HPK1, also called MAP4K1) negatively regulates T cell-mediated immune responses. However, the role of HPK1 and the mechanisms that regulate HPK1 expression in SLE remain poorly understood. Using chromatin immunoprecipitation (ChIP) microarray data, we identified markedly increased histone H3 lysine 27 trimethylation (H3K27me3) enrichment at the HPK1 promoter of SLE CD4+ T cells relative to controls, and confirmed this observation using ChIP and real-time PCR experiments. We further found that HPK1 mRNA and protein levels were s... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5382200 Mon, 17 Oct 2011 04:00:00 +0100 5382200 http://www.medworm.com/index.php?rid=5382201&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22004905%26dopt%3DAbstract Authors: Munoz-Suano A, Kallikourdis M, Sarris M, Betz AG Abstract Pregnancy frequently has a beneficial effect on the autoimmune disease Rheumatoid Arthritis, ranging from improvement in clinical symptoms to complete remission. Despite decades of study, a mechanistic explanation remains elusive. Here, we demonstrate that an analogous pregnancy-induced remission can be observed in a mouse model of arthritis. We demonstrate that during pregnancy mice are protected from collagen-induced arthritis, but are still capable of launching normal immune responses to influenza infections. We examine the role of regulatory T (T(R)) cells in this beneficial effect. T(R) cells are essential for many aspects of immune tolerance, including the suppression of autoimmune responses. Remarkably, trans... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5382201 Sat, 15 Oct 2011 04:00:00 +0100 5382201 http://www.medworm.com/index.php?rid=5314459&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982749%26dopt%3DAbstract Authors: Kihara M, Leroy V, Baudino L, Evans LH, Izui S Abstract The envelope glycoprotein gp70 of endogenous retroviruses implicated in murine lupus nephritis is secreted by hepatocytes and its expression is controlled by Sgp3 (serum gp70 production 3) and Sgp4 loci derived from lupus-prone mice. Among three different endogenous retroviruses (ecotropic, xenotropic and polytropic), xenotropic viruses are considered to be the major source of serum gp70. Although the abundance of xenotropic viral gp70 RNA in livers was up-regulated by the presence of these two Sgp loci, it has not yet been clear whether Sgp3 and Sgp4 regulate the expression of a fraction or multiple xenotropic viruses present in mouse genome. To address this question, we determined the genetic origin of xenotropic vi... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5314459 Fri, 07 Oct 2011 04:00:00 +0100 5314459 http://www.medworm.com/index.php?rid=5282669&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21959269%26dopt%3DAbstract In this study we found that a subset of human CD4(+) T cells expressing MCAM (CD146) have higher mRNA levels of RORC2, IL-23R, IL-26, IL-22, IL-17A, but not IFN-γ, compared to CD4(+) T cell not expressing CD146. Upon TCR stimulation with CD3/CD28, CD4(+)CD146(+) T cells secrete significantly more IL-17A, IL-6, and IL-8 than do CD4(+)CD146(-) T cells. Low frequencies of CD4(+)CD146(+) T cells are found in the circulation of healthy adults, but the frequency of these cells is significantly increased in the circulation of patients with inflammatory autoimmune diseases including Behcet's, sarcoidosis and Crohn's disease. Patterns of gene expression and cytokine secretion in these cells are similar in healthy and disease groups. In Crohn's disease, the increase in CD4(+)CD146(+) cells in the ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5282669 Wed, 28 Sep 2011 04:00:00 +0100 5282669 http://www.medworm.com/index.php?rid=5282668&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962567%26dopt%3DAbstract Authors: Piconese S, Costanza M, Tripodo C, Sangaletti S, Musio S, Pittoni P, Poliani PL, Burocchi A, Passafaro AL, Gorzanelli A, Vitali C, Chiodoni C, Barnaba V, Pedotti R, Colombo MP Abstract Lymphnode swelling during immune responses is a transient, finely regulated tissue rearrangement, accomplished with the participation of the extracellular matrix. Here we show that murine and human reactive lymph nodes express SPARC in the germinal centres. Defective follicular dendritic cell networking in SPARC-deficient mice is accompanied by a severe delay in the arrangement of germinal centres and development of humoral autoimmunity, events that are linked to Th17 development. SPARC is required for the optimal and rapid differentiation of Th17 cells, accordingly we show delayed developme... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5282668 Wed, 28 Sep 2011 04:00:00 +0100 5282668 http://www.medworm.com/index.php?rid=5249393&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924866%26dopt%3DAbstract In this study, we analyzed BC-patterns and BC-immunoreactivity at these sites during active and during stable disease and the impact of disease modifying drugs (DMD) on peripheral BC-homeostasis. For this purpose we assessed BC-subsets in blood and CSF from patients with clinically isolated syndrome (CIS), relapsing remitting MS (RRMS), rheumatoid arthritis (RA), and healthy controls (HC) by flow cytometric detection of whole (W-BC), naïve, transitional (TN-BC), class-switched memory (CSM-BC), unswitched memory (USM-BC), double-negative memory (DNM-BC) BC-phenotypes, plasma blasts (PB), and plasma cells (PC). FACS-data were correlated with BC-specific chemotactic activities in CSF, intrathecal CXCL13-levels, and immunoreactivity of peripheral W-BC. Our study revealed that frequencies of s... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5249393 Thu, 15 Sep 2011 04:00:00 +0100 5249393 http://www.medworm.com/index.php?rid=5220200&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907543%26dopt%3DAbstract Authors: Borchers AT, Leibushor N, Cheema GS, Naguwa SM, Gershwin ME Abstract Biological agents represent a major advance in the treatment of rheumatic diseases, most particularly in the prevention of irreversible structural damage. While generally well tolerated, their increasing use continues to reveal a variety of immune-mediated adverse effects. The most frequent adverse events are infusion reactions and injection site reactions, but despite their fairly common occurrence the precise mechanisms are not fully understood. Another adverse event that became appreciated early in the era of biologicals is the increased risk of Mycobacterium tuberculosis and other granulomatous infections in patients treated with tumor necrosis factor (TNFα) antagonists. Although it is evident that t... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5220200 Thu, 08 Sep 2011 04:00:00 +0100 5220200 http://www.medworm.com/index.php?rid=5220201&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880464%26dopt%3DAbstract Authors: Rogers MA, Levine DA, Blumberg N, Fisher GG, Kabeto M, Langa KM Abstract Infection has long been implicated as a trigger for autoimmune disease. Other antigenic challenges include receipt of allogeneic tissue or blood resulting in immunomodulation. We investigated antigenic challenges as possible risk factors for autoimmune disease in women using the Health and Retirement Study, a nationally representative longitudinal study, linked to Medicare files, years 1991-2007. The prevalence of autoimmune disease (rheumatoid arthritis, Hashimoto's disease, Graves' disease, systemic lupus erythematosus, celiac disease, systemic sclerosis, Sjögren syndrome and multiple sclerosis) was 1.4% in older women (95% CI: 1.3%, 1.5%) with significant variation across regions of the United Sta... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5220201 Mon, 29 Aug 2011 04:00:00 +0100 5220201 http://www.medworm.com/index.php?rid=5179467&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872430%26dopt%3DAbstract In conclusion, we demonstrated that only 3 immunodominant epitopes are targeted by ACPA on citrullinated fibrin stressing their actual oligoclonality. However, the reactivity to the 3 epitopes distinguishes three subgroups of patients. The closely restricted antigen specificity suggests that the autoimmune reaction to citrullinated fibrin is antigen-driven. The accessibility of the epitopes reinforces the hypothesis of a pathogenic role for ACPA via immune complexe formation in the synovial tissue. PMID: 21872430 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5179467 Wed, 24 Aug 2011 23:00:00 +0100 5179467 http://www.medworm.com/index.php?rid=5179468&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868195%26dopt%3DAbstract This study was undertaken to investigate the hypothesis that microbial peptides bind HLA-DR3 and activate T cells reactive with lupus autoantigens. Using HLA-DR3 transgenic mice and lupus-associated autoantigen SmD protein, SmD(79-93) was identified to contain a dominant HLA-DR3 restricted T cell epitope. This T cell epitope was characterized by using a T-T hybridoma, C1P2, generated from SmD immunized HLA-DR3 transgenic mouse. By pattern search analysis, 20 putative mimicry peptides (P2-P21) of SmD(79-93,) from microbial and human origin were identified. C1P2 cells responded to SmD, SmD(79-93) and a peptide (P20) from Vibro cholerae. Immunization of HLA-DR3 mice with P20 induced T cell responses and IgG antibodies to SmD that were not cross-reactive with the immunogen. A T-T hybridoma, P2... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5179468 Mon, 22 Aug 2011 23:00:00 +0100 5179468 http://www.medworm.com/index.php?rid=5106968&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21813263%26dopt%3DAbstract Authors: Jørgensen KT, Pedersen BV, Nielsen NM, Jacobsen S, Frisch M To evaluate the possible biological role of pregnancy on the risk of autoimmune diseases we assessed associations between reproductive history and subsequent risk of autoimmune diseases characterized by female predominance and other autoimmune diseases. Our study cohort comprised 4.6 million Danes born since 1935 for whom a complete record of childbirths was available. Cohort members were followed for hospital contacts for 31 autoimmune diseases from 1982 to 2008. Female predominant autoimmune diseases were those with a female:male sex ratio >2:1. Ratios of first hospitalization rates were calculated using Poisson regression, adjusting for potential confounding by age, birth cohort, calendar period and marital sta... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5106968 Sun, 31 Jul 2011 23:00:00 +0100 5106968 http://www.medworm.com/index.php?rid=5106969&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795021%26dopt%3DAbstract Authors: Hintermann E, Holdener M, Bayer M, Loges S, Pfeilschifter JM, Granier C, Manns MP, Christen U Autoimmune hepatitis (AIH) is a serious chronic inflammatory disease of the liver with yet unknown etiology and largely uncertain immunopathology. The hallmark of type 2 AIH is the generation of liver kidney microsomal-1 (LKM-1) autoantibodies, which predominantly react to cytochrome P450 2D6 (CYP2D6). The identification of disease initiating factors has been hampered in the past, since antibody epitope mapping was mostly performed using serum samples collected late during disease resulting in the identification of immunodominant epitopes not necessarily representing those involved in disease initiation. In order to identify possible environmental triggers for AIH, we analyzed for the... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5106969 Sun, 24 Jul 2011 23:00:00 +0100 5106969 http://www.medworm.com/index.php?rid=5106970&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21788115%26dopt%3DAbstract Authors: Landek-Salgado MA, Rose NR, Caturegli P Pregnancy modulates autoimmune diseases through diverse and still incompletely defined mechanisms, in part operating at the decidua-placenta interface. To assess the immunological contribution of placenta, we administered mouse placental proteins to a mouse model of autoimmune hypophysitis, a disease known to be strongly associated with pregnancy. Emulsified placental proteins suppressed both the cellular and humoral aspects of hypophysitis. Suppression was specific to self antigens and not seen when two foreign antigens, tetanus toxoid or tuberculin purified protein derivative, were used. Proteomic analysis revealed high levels of soluble TNF receptor 1 in placenta, suggesting that blockade of the TNF-α pathway was a mechanism of disea... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5106970 Fri, 22 Jul 2011 23:00:00 +0100 5106970 http://www.medworm.com/index.php?rid=5062718&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763105%26dopt%3DAbstract Authors: Naiyanetr P, Butler JD, Meng L, Pfeiff J, Kenny TP, Guggenheim KG, Reiger R, Lam K, Kurth MJ, Ansari AA, Coppel RL, López-Hoyos M, Gershwin ME, Leung PS Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure-activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coup... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5062718 Wed, 13 Jul 2011 23:00:00 +0100 5062718 http://www.medworm.com/index.php?rid=5062719&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752599%26dopt%3DAbstract In this study we analyzed and compared the in situ pathological manifestations of EAE utilizing two different models, namely the relapsing-remitting PLP-induced and the chronic MOG-induced diseases. To characterize pathological changes, both transmission electron microscopy (TEM) and immunohistochemistry were employed. The effect of the approved MS drug glatiramer acetate (GA, Copaxone) on myelin damage/repair and on motor neuron loss/preservation was studied in both EAE models. Ultrastructural spinal cord analysis revealed multiple white matter damage foci, with different patterns in the two EAE models. Thus, the relapsing-remitting model was characterized mainly by widespread myelin damage and by remyelinating fibers, whereas in the chronic model axonal degeneration was more prevalent. L... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5062719 Sun, 10 Jul 2011 23:00:00 +0100 5062719 http://www.medworm.com/index.php?rid=5062720&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21745722%26dopt%3DAbstract Authors: Li CR, Deiro MF, Godebu E, Bradley LM Type 1 diabetes (T1D) develops as a consequence of a progressive autoimmune response that destroys insulin-producing β-cells in pancreatic islets. Because of their role(s) in controlling immune responses, considerable effort has been directed toward resolving whether regulatory T cells (Tregs) offer a clinical treatment to restore tolerance in T1D. We previously reported that in vitro-induced adaptive Treg cells (aTregs) can reverse T1D and persist as protective memory cells in the NOD mouse model. In the current study, we investigated mechanisms that regulate aTregs. We found that these FoxP3(+) aTregs expressed high levels of the IL-7 receptor, IL-7Rα, without the high affinity receptor for IL-2, CD25, which is found on natural Treg c... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5062720 Fri, 08 Jul 2011 23:00:00 +0100 5062720 http://www.medworm.com/index.php?rid=5011328&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21700422%26dopt%3DAbstract In this study, we describe an essential mechanism by which the actin regulatory protein Coronin 1A (Coro1A) ensures the proper response of Th17 CD4(+) T cells to TGFβ. Coro1A has been established as a key player in T cell survival, migration, activation, and Ca(2+) regulation in naive T cells. We show that mice lacking Coro1a developed less severe experimental autoimmune encephalomyelitis (EAE). Unexpectedly, upon the re-induction of EAE, Coro1a(-/-) mice exhibited enhanced EAE signs that correlated with increased numbers of IL-17 producing CD4(+) cells in the central nervous system (CNS) compared to wild-type mice. In vitro differentiated Coro1a(-/-) Th17 CD4(+) T cells consistently produced more IL-17 than wild-type cells and displayed a Th17/Th1-like phenotype in regard to the expressi... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=5011328 Mon, 20 Jun 2011 23:00:00 +0100 5011328 http://www.medworm.com/index.php?rid=4963101&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689905%26dopt%3DAbstract Authors: Wang YL, Chou FC, Chen SJ, Lin SH, Chang DM, Sytwu HK The pre-ligand assembly domain (PLAD) of tumor necrosis factor receptors mediates specific ligand-independent receptor assembly and subsequent signaling. However, the physiological role of PLAD in the regulation of TNFR-mediated immune responses in autoimmunity is still unclear. By using the recombinant PLAD.Fc protein to block TNFR1 assembly, we demonstrated that PLAD.Fc treatment significantly reduced the TNFR1-driving proinflammatory cytokines and protected NOD mice from diabetes. Strikingly, Th17 differentiation was significantly inhibited in PLAD.Fc-treated NOD and TNFR1-deficient mice, indicating a TNFR1-dependent Th17 development. PLAD.Fc-modulated effects on DCs, in terms of the downregulation of Th17-inducing cytok... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963101 Fri, 17 Jun 2011 23:00:00 +0100 4963101 http://www.medworm.com/index.php?rid=4963100&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689906%26dopt%3DAbstract Authors: Séité JF, Guerrier T, Cornec D, Jamin C, Youinou P, Hillion S One way for intravenous Ig (IVIg) to affect responses of the B cells might be to operate through their TLR7 and TLR9. We confirm the ability of TLR agonists to induce CD25 expression in B cells. For this to occur, sialylated Fc-gamma of IgG included in the IVIg preparation are required. As a result, IVIg suppresses TLR-induced production of the proinflammatory IL-6, but not that of the anti-inflammatory IL-10. That is, IVIg mimics the effects of the MyD88 inhibitor. Finally, as we previously showed that IVIg induces CD22 to recruit the inhibitory SHP-1, we established that this enzyme was also involved in IVIg-induced inhibition of TLR9 signaling. This is the first report to demonstrate such a mechanism underlying... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963100 Fri, 17 Jun 2011 23:00:00 +0100 4963100 http://www.medworm.com/index.php?rid=4963103&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21683550%26dopt%3DAbstract Authors: Rose NR Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963103 Tue, 14 Jun 2011 23:00:00 +0100 4963103 http://www.medworm.com/index.php?rid=4963102&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21683551%26dopt%3DAbstract Authors: Kong YC, Brown NK, Flynn JC, McCormick DJ, Brusic V, Morris GP, David CS Thyroglobulin (Tg), a homodimer of 660 kD comprising 2748 amino acids, is the largest autoantigen known. The prevalence of autoimmune thyroid disease, including Hashimoto's thyroiditis and Graves' disease, has provided the impetus for identifying pathogenic T cell epitopes from human Tg over two decades. With no known dominant epitopes, the search has long been a challenge for investigators. After identifying HLA-DRB1∗03:01 (HLA-DR3) and H2E(b) as susceptibility alleles for Tg-induced experimental autoimmune thyroiditis in transgenic mouse strains, we searched for naturally processed T cell epitopes with MHC class II-binding motif anchors and tested the selected peptides for pathogenicity in these mice... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963102 Tue, 14 Jun 2011 23:00:00 +0100 4963102 http://www.medworm.com/index.php?rid=4963104&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21680149%26dopt%3DAbstract Authors: Ali F, Rowley M, Jayakrishnan B, Teuber S, Gershwin ME, Mackay IR Stiff Person Syndrome (SPS) is a rare autoimmune neurological disease attributable to autoantibodies to glutamic acid decarboxylase (anti-GAD) more usually associated with the islet beta cell destruction of autoimmune type 1 diabetes (T1D). SPS is characterized by interference in neurons with the synthesis/activity of the inhibitory neurotransmitter gamma amino butyric acid (GABA) resulting in the prototypic progressive spasmodic muscular rigidity of SPS, or diverse neurological syndromes, cerebellar ataxia, intractable epilepsy, myoclonus and several others. Remarkably, a single autoantibody, anti-GAD, can be common to widely different disease expressions, i.e. T1D and SPS. One explanation for these data is the... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963104 Mon, 13 Jun 2011 23:00:00 +0100 4963104 http://www.medworm.com/index.php?rid=4963106&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21665435%26dopt%3DAbstract Authors: Behrens M, Smart M, Luckey D, Luthra H, Taneja V Population studies have shown that amongst all the genetic factors linked with autoimmune disease development, MHC class II genes are the most significant. Experimental autoimmune arthritis resembling human rheumatoid arthritis (RA) can be induced in susceptible strains of mice following immunization with type II collagen (CIA). We generated transgenic mice lacking endogenous class II molecules and expressing various HLA genes including RA-associated, HLA-DRB1*0401 and HLA-DQ8, and RA-resistant, DRB1*0402, genes. The HLA molecules in these mice are expressed on the cell surface and can positively select CD4+ T cells expressing various Vβ T cell receptors. Endogenous class II invariant chain is required for proper functioning of... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963106 Thu, 09 Jun 2011 23:00:00 +0100 4963106 http://www.medworm.com/index.php?rid=4963105&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21665436%26dopt%3DAbstract Authors: Santiago-Raber ML, Baudino L, Alvarez M, van Rooijen N, Nimmerjahn F, Izui S Circulating monocytes are divided into two major, phenotypically and functionally distinct subsets: Gr-1(hi) "inflammatory" and Gr-1(lo) "resting" monocytes. One of the unique cellular abnormalities in lupus-prone mice is monocytosis, which is characterized by a selective expansion of Gr-1(lo) monocytes and dependent on the expression of stimulatory IgG Fc receptors (FcγR). We speculated that IgG immune complexes containing nuclear antigens could stimulate Gr-1(hi) monocytes through interaction with FcγRs and then TLR7 and TLR9, thereby promoting the maturation towards Gr-1(lo) monocytes. In the present study, we assessed this hypothesis by analyzing effects of TLR9 or TLR7 agonist on monocytes in ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963105 Thu, 09 Jun 2011 23:00:00 +0100 4963105 http://www.medworm.com/index.php?rid=4963107&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664106%26dopt%3DAbstract Authors: Gleicher N, Weghofer A, Barad DH There, likely, is no more controversial issue in reproductive medicine than the effects of autoimmunity on female reproductive success. Published studies are, therefore, often biased. We performed PubMed, Google Scholar and Medline searches for the years 2000-2010 under various key words and phrases, referring to effects of autoimmunity/autoimmune diseases on pregnancy/pregnancy outcomes/pregnancy rates/reproduction/reproductive outcomes/fertility/infertility/fertility treatments/infertility treatments, and a number of similar terms. Reference lists of selected manuscripts were evaluated for additional, potential references. All selected manuscripts were reviewed by at least one author (N.G.). Opinions were reached based on preferential review ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4963107 Tue, 07 Jun 2011 23:00:00 +0100 4963107 http://www.medworm.com/index.php?rid=4815803&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561736%26dopt%3DAbstract Authors: Koh AE, Njoroge SW, Feliu M, Cook A, Selig MK, Latchman YE, Sharpe AH, Colvin RB, Paul E Polymorphisms in the SLAM family of leukocyte cell surface regulatory molecules have been associated with lupus-like phenotypes in both humans and mice. The murine Slamf gene cluster lies within the lupus-associated Sle1b region of mouse chromosome 1. Non-autoreactive C57BL/6 (B6) mice that have had this region replaced by syntenic segments from other mouse strains (i.e. 129, NZB and NZW) are B6 congenic strains that spontaneously produce non-nephritogenic lupus-like autoantibodies. We have recently reported that genetic ablation of the SLAM family member CD48 (Slamf2) drives full-blown autoimmune disease with severe proliferative glomerulonephritis (CD48GN) in B6 mice carrying 129 sequenc... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4815803 Sun, 08 May 2011 23:00:00 +0100 4815803 http://www.medworm.com/index.php?rid=4815804&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524885%26dopt%3DAbstract Authors: Blank M, Baraam L, Eisenstein M, Fridkin M, Dardik R, Heldman Y, Katchalski-Katzir E, Shoenfeld Y Antiphospholipid syndrome (APS) is characterized by thromboembolic phenomena and recurrent fetal loss associated with elevated circulating anti-phospholipid/beta2glycoprotein-I(β2GPI)-binding-antibodies(Abs) . Individual APS patients harbor diverse clusters of circulating anti-β2GPI Abs, targeting different epitopes on the β2GPI molecule. Our novel approach was to construct a peptide composed of β2GPI-ECs-binding-site (phospholipids-membrane), named "EMBI". EMBI exert dual activities: a) At first EMBI prevented β2GPI ECs binding, thus reduced by 89% the binding of β2GPI/anti-β2GPI to the cells in comparison with 9.3% inhibition by EMBI scrambled form (scEMBI). b) Longer exp... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4815804 Sun, 24 Apr 2011 23:00:00 +0100 4815804 http://www.medworm.com/index.php?rid=4815805&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497486%26dopt%3DAbstract Authors: Kaminitz A, Yolcu ES, Stein J, Yaniv I, Shirwan H, Askenasy N We hypothesized that regulatory T cells (Treg) effectively target diabetogenic cells, and reinforcing their killing capacity will attenuate the course of disease. For proof of concept, Fas-ligand (FasL) protein was conjugated to CD25(+) Treg (killer Treg) to simulate the physiological mechanism of activation-induced cell death. Cytotoxic and suppressive activity of killer Treg was superior to naïve Treg in vitro. Administration of 3-4 × 10(6) Treg prevented hyperglycemia in 65% prediabetic NOD females, however only killer Treg postponed disease onset by 14 weeks. CD25(+) Treg homed to the pancreas and regional lymph nodes of prediabetic NOD females, proliferated and ectopic FasL protein induced apoptosis in CD25... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4815805 Wed, 13 Apr 2011 23:00:00 +0100 4815805 http://www.medworm.com/index.php?rid=4710524&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21486688%26dopt%3DAbstract Authors: Hegde S, Lockridge JL, Becker YA, Ma S, Kenney SC, Gumperz JE NKT cells are innate lymphocytes that can recognize self or foreign lipids presented by CD1d molecules. NKT cells have been shown to inhibit the development of autoimmunity in murine model systems, however, the pathways by which they foster immune tolerance remain poorly understood. Here we show that autoreactive human NKT cells stimulate monocytes to differentiate into myeloid APCs that have a regulatory phenotype characterized by poor conjugate formation with T cells. The NKT cell instructed myeloid APCs show elevated expression of the inhibitory ligand PD-L2, and blocking PD-L1 and PD-L2 during interactions of the APCs with T cells results in improved cluster formation and significantly increased T cell prolifera... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4710524 Sat, 09 Apr 2011 23:00:00 +0100 4710524 http://www.medworm.com/index.php?rid=4710525&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21458954%26dopt%3DAbstract In this study, we show that receptor editing fails to be induced in antigen-activated DNA-reactive B cells that overexpress Bcl-2 (Bcl-2 Tg). The failure to induce RAG and receptor editing is likely due, at least partially, to the lack of self antigen. First, the levels of circulating DNA and of apoptotic bodies in the spleen of Bcl-2 Tg mice are significantly lower than in control mice. Second, in Bcl-2 Tg mice, RAG can be induced in a population of antigen-activated B cells by providing exogenous soluble antigen. These data suggest that, in addition to its anti-apoptotic activity, Bcl-2 may indirectly inhibit tolerance induction in B cells acquiring anti-nuclear antigen reactivity after peripheral activation by limiting the availability of self antigen. PMID: 21458954 [PubMed - as su... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4710525 Wed, 30 Mar 2011 23:00:00 +0100 4710525 http://www.medworm.com/index.php?rid=4655454&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21441014%26dopt%3DAbstract Authors: Thangavelu G, Parkman JC, Ewen CL, Uwiera RR, Baldwin TA, Anderson CC Lymphopenia driven T cell activation is associated with autoimmunity. That lymphopenia does not always lead to autoimmunity suggests that control mechanisms may exist. We assessed the importance of the co-inhibitory receptor programmed death-1 (PD-1) in the control of lymphopenia-driven autoimmunity in newly generated T cells vs. established peripheral T cells and in thymic selection. PD-1 was not required for negative selection in the thymus or for maintenance of self tolerance following transfer of established PD-1(-/-) peripheral T cells to a lymphopenic host. In contrast, PD-1 was essential for systemic self tolerance in newly generated T cells under lymphopenic conditions, as PD-1(-/-) recent thymic emi... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4655454 Fri, 25 Mar 2011 00:00:00 +0100 4655454 http://www.medworm.com/index.php?rid=4655456&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439785%26dopt%3DAbstract Authors: Baugh M, Black D, Westwood P, Kinghorn E, McGregor K, Bruin J, Hamilton W, Dempster M, Claxton C, Cai J, Bennett J, Long C, McKinnon H, Vink P, Hoed LD, Gorecka M, Vora K, Grant E, Percival MD, Boots AM, van Lierop MJ The purpose of the study was to examine the potential of inhibition of cathepsin S as a treatment for autoimmune diseases. A highly selective cathepsin S inhibitor, CSI-75, was shown to upregulate levels of the cathepsin S substrate, invariant chain Lip10, in vitro as well as in vivo in C57Bl/6 mice after oral administration. Functional activity of the compound was shown by a reduction in the OVA-specific response of OVA-sensitized splenocytes from C57Bl/6 mice as well as from OVA-TCR transgenic mice (DO11.10). Since these studies revealed a selective suppression... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4655456 Wed, 23 Mar 2011 00:00:00 +0100 4655456 http://www.medworm.com/index.php?rid=4655455&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439786%26dopt%3DAbstract Authors: Hoffmann MH, Skriner K, Herman S, Baumann C, Steiner CW, Ospelt C, Meyer B, Gleiss A, Pfatschbacher J, Niederreiter B, Tuncel J, Zanoni G, Steiner G Autoimmune responses to heterogeneous nuclear ribonucleproteins (hnRNP) occur in many systemic autoimmune diseases, particularly in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. In RA, humoral and/or cellular autoimmunity to hnRNP-A2/B1 is the most prominent anti-nuclear reactivity, being detectable in more than 50% of patients. However, its pathogenic role has not been fully elucidated yet. Here, we report that splenocytes from rats with pristane-induced arthritis transfer disease after in vitro restimulation with hnRNP-A/B antigens. Remarkably, disease transfer can be blocked by nuclease treatment of ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4655455 Wed, 23 Mar 2011 00:00:00 +0100 4655455 http://www.medworm.com/index.php?rid=4655458&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21414755%26dopt%3DAbstract This study therefore assigns a novel role to IL-18 for expanding the pool of islet-destructive T cells during pre-diabetes. This report highlights a new basic mechanism in type 1 diabetes pathogenesis and suggests that targeting the IL-18 pathway should be explored as a potential treatment strategy. PMID: 21414755 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4655458 Tue, 15 Mar 2011 00:00:00 +0100 4655458 http://www.medworm.com/index.php?rid=4655457&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21414756%26dopt%3DAbstract CONCLUSIONS: In highly specific fetal/maternal combinations, maternal T cells with activity against the offspring pancreatic beta cells, presumably chimeric in fetal organs, initiate islet inflammation and may therefore predispose to auto-immune diabetes. PMID: 21414756 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4655457 Tue, 15 Mar 2011 00:00:00 +0100 4655457 http://www.medworm.com/index.php?rid=4593097&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21396797%26dopt%3DAbstract Authors: Haylock-Jacobs S, Comerford I, Bunting M, Kara E, Townley S, Klingler-Hoffmann M, Vanhaesebroeck B, Puri KD, McColl SR The Class IA phosphoinositide 3-kinase delta (PI3Kδ) has been implicated in multiple signaling pathways involved in leukocyte activation and hence is an attractive target in many human autoimmune diseases, including multiple sclerosis (MS). Here, using mice expressing a catalytically inactive form of the PI3Kδ subunit p110δ, we show that signaling through PI3Kδ is required for full and sustained pathology of experimental autoimmune encephalomyelitis (EAE), a Th17-driven model of MS. In p110δ-inactivated mice, T cell activation and function during EAE was markedly reduced and fewer T cells were observed in the central nervous system (CNS). The decrease in ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4593097 Wed, 09 Mar 2011 00:00:00 +0100 4593097 http://www.medworm.com/index.php?rid=4593098&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21377836%26dopt%3DAbstract In this study, the role of activin, a member of the TGF-β superfamily, was investigated in the pathogenesis of fibrosis in SSc. Serum activin A levels in patients with SSc were measured by ELISA, and the expression of the activin receptor type IB (ACVRIB/ALK4) and the activity of the signaling pathway via ACVRIB/ALK4 were investigated using western blotting. To evaluate a potential therapeutic strategy for SSc, we also attenuated the ACVRIB/ALK4 pathway using an inhibitor. Serum activin A levels were significantly higher in SSc patients than in normal controls. Activin A and ACVRIB/ALK4 expression were also higher in cultured SSc fibroblasts. Activin A stimulation induced phosphorylation of Smad2/3 and CTGF expression in SSc fibroblasts. Procollagen production and Col1α mRNA also increas... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4593098 Fri, 04 Mar 2011 00:00:00 +0100 4593098 http://www.medworm.com/index.php?rid=4593101&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376533%26dopt%3DAbstract Authors: Cauwe B, Martens E, Sagaert X, Dillen C, Geurts N, Li S, Mertens J, Thijs G, Van den Steen PE, Heremans H, De Vos R, Blockmans D, Arnold B, Opdenakker G Gelatinase B/matrix metalloproteinase-9 (MMP-9) is a key enzyme involved in inflammatory, hematological, vascular and neoplastic diseases. In previous studies, we explored the intracellular substrate set or 'degradome' of MMP-9 and found many systemic autoantigens as novel intracellular gelatinase B substrates. Little is known, however, about the functional role of MMP-9 in the development of systemic autoimmunity in vivo. B6(lpr/lpr) mice with defective Fas-mediated apoptosis were used to investigate the functions of MMP-9 in lymphocyte proliferation and in the development of systemic autoimmunity. Combined Fas and gelatinas... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4593101 Wed, 02 Mar 2011 00:00:00 +0100 4593101 http://www.medworm.com/index.php?rid=4593100&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376534%26dopt%3DAbstract Authors: Ullal AJ, Reich CF, Clowse M, Criscione-Schreiber LG, Tochacek M, Monestier M, Pisetsky DS Systemic lupus erythematosus is a prototypic autoimmune disease characterized by antibodies to DNA and other nuclear molecules. While these antibodies can form immune complexes, the mechanisms generating the bound nuclear antigens are not known. These studies investigated whether microparticles can form complexes with anti-DNA and other anti-nucleosomal antibodies. Microparticles are small membrane-bound vesicles released from dead and dying cells; these particles contain a variety of cellular components, including DNA. To assess antigenicity, microparticles generated in vitro from apoptotic cell lines were tested using murine monoclonal anti-DNA and anti-nucleosomal antibodies as well a... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4593100 Wed, 02 Mar 2011 00:00:00 +0100 4593100 http://www.medworm.com/index.php?rid=4593099&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376535%26dopt%3DAbstract This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period in children genetically predisposed to type 1 diabetes. Between 1989 and 2010, children who were first-degree relatives of patients with type 1 diabetes and who were born in Germany were prospectively followed from birth without intervention. A total of 324 children (BABYDIAB study) born between 1989 and 2000 and 216 children (TEDDY study) born between 2004 and 2010 with matched HLA genotypes were recruited before age 3 months and included for analysis. Children were followed for the development of autoantibodies to insulin, GAD, and IA-2, and for progression to diabetes. The cumulative frequency of diabetes by age 4 years ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4593099 Wed, 02 Mar 2011 00:00:00 +0100 4593099 http://www.medworm.com/index.php?rid=4534232&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354768%26dopt%3DAbstract Authors: Ruiz-Riol M, Armengol Barnils MD, Colobran Oriol R, Sánchez Pla A, Borràs Serres FE, Lucas-Martin A, Martínez Cáceres EM, Pujol-Borrell R Graves' disease (GD) is a chronic autoimmune process in the thyroid gland and involves IFN and IFN driven immune activation. Assuming the thyroid gland is the main site stimulating the autoimmune response, we investigated the role of IFNs and other factors in the chronic evolution of GD by comparing the transcriptomic profiles of thyroid glands from short clinical course (SC), long clinical course (LC) cases, and control glands (C). Over 200 differentially expressed genes of the immune system were identified. Results were extensively analyzed bioinformatically and validated by qPCR in 31 glands. The analysis indicated that GD involved a ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4534232 Fri, 25 Feb 2011 00:00:00 +0100 4534232 http://www.medworm.com/index.php?rid=4534234&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333491%26dopt%3DAbstract Authors: Fousteri G, Dave A, Morin B, Omid S, Croft M, von Herrath MG Myocarditis poses a severe health problem, can lead to dilated cardiomyopathy (DCM) and death, and is thought to be triggered by infections. Enteroviruses such as Coxsackie virus B 3 (CVB3) have been implicated as a culprit, since they can cause acute and chronic heart disease in susceptible mice. CVB was detected in human cardiac myocytes in some cases, whereas acute CVB infection was thought to have caused death. Here we studied, whether nasal administration of cardiac myosin (CM) major histocompatibility class (MHC) II peptides CM(947-960) and CM(735-747) and OX40 blockade would be able to ameliorate immunopathology and heart disease in BALB/C mice infected with CVB3. We found that nasal CM-peptide prophylactic tr... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4534234 Wed, 16 Feb 2011 00:00:00 +0100 4534234 http://www.medworm.com/index.php?rid=4534233&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333492%26dopt%3DAbstract Authors: Kampylafka EI, Routsias JG, Alexopoulos H, Dalakas MC, Moutsopoulos HM, Tzioufas AG The autoantibody to aquaporin-4 (AQP4) is a marker and a pathogenetic factor in Neuromyelitis Optica (NMO) (Devic's syndrome). Our aim was to identify B-cell antigenic linear epitopes of the AQP4 protein and investigate similarities with other molecules. To this end, we screened sera from 21 patients positive for anti-AQP4 antibodies (study group), from 23 SLE and 23 pSS patients without neurologic involvement (disease controls) and from 28 healthy individuals (normal controls). Eleven peptides, spanning the entire intracellular and extracellular domains of the AQP4 molecule, were synthesized, and all sera were screened for anti-peptide antibodies by ELISA. Specificity was evaluated by homologo... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4534233 Wed, 16 Feb 2011 00:00:00 +0100 4534233 http://www.medworm.com/index.php?rid=4480908&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316922%26dopt%3DAbstract This study reports that regulation of T cell responses can be induced by B cells following CD40-dependent cognate interaction. T cell proliferation and cytokine production were differentially regulated. Thus, CD40-induced regulatory B cells partially inhibited T cell proliferation following CD40 interaction without requirement of soluble factor. In contrast, modulation of Th1 differentiation resulted from CD80- and CD86-dependent interactions and from IL-10 production. The suppressive effects were mediated by CD19(high)IgD(+)CD38(high)CD24(high)CD5(high) B cells and appeared to be indirect, through the induction of regulatory T cells as indicated by the appearance of Foxp3(+)CD4(+)CD25(+)T cells. These data suggest that activation signals from T cells initiate regulatory properties in B ce... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4480908 Fri, 11 Feb 2011 00:00:00 +0100 4480908 http://www.medworm.com/index.php?rid=4480909&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21282039%26dopt%3DAbstract Authors: Sharma R, Fu SM, Ju ST CD4(+) T-cell (Th) cytokines provide important regulatory and effector functions of T-cells. Among them, IL-2 plays a unique role. IL-2 is required for the generation and maintenance of regulatory T-cells (Treg) to provide lifelong protection from autoimmune disease. Whether IL-2 is also required for autoimmune disease development is less clear as Il2(-/)(-) mice themselves spontaneously develop multi-organ inflammation (MOI). In this communication, we discuss evidence that support the thesis that IL-2 is required for the development of autoimmune response, although some aspects of autoimmune response are not regulated by IL-2. Potential IL-2-dependent mechanisms operating at specific stages of the inflammation process are presented. The interplays among... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4480909 Sat, 29 Jan 2011 00:00:00 +0100 4480909 http://www.medworm.com/index.php?rid=4414302&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21273044%26dopt%3DAbstract Authors: Richards MH, Getts MT, Podojil JR, Jin YH, Kim BS, Miller SD Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) serves as virus-induced model of chronic progressive multiple sclerosis. Infection of susceptible SJL/J mice leads to life-long CNS virus persistence and a progressive autoimmune demyelinating disease mediated by myelin-specific T cells activated via epitope spreading. In contrast, virus is rapidly cleared by a robust CTL response in TMEV-IDD-resistant C57BL/6 mice. We investigated whether differential induction of regulatory T cells (Tregs) controls susceptibility to TMEV-IDD. Infection of disease-susceptible SJL/J, but not B6 mice, leads to rapid activation and expansion of Tregs resulting in an unfavorable CNS ratio of Treg:Te... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4414302 Tue, 25 Jan 2011 00:00:00 +0100 4414302 http://www.medworm.com/index.php?rid=4350094&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216565%26dopt%3DAbstract Authors: Göbel K, Pankratz S, Schneider-Hohendorf T, Bittner S, Schuhmann MK, Langer HF, Stoll G, Wiendl H, Kleinschnitz C, Meuth SG Disruption of the blood brain barrier (BBB) and transendothelial trafficking of immune cells into the central nervous system (CNS) are pathophysiological hallmarks of Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE). Kinins are proinflammatory peptides which are released during tissue injury including EAE. They increase vascular permeability and enhance inflammation by acting on distinct bradykinin receptors, B1R and B2R. We studied the expression of B1R and B2R and the effect of their inhibition on the disease course, BBB integrity and T cell migration following myelin oligodendrocyte glycoprotein (MOG(35-55... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4350094 Fri, 07 Jan 2011 00:00:00 +0100 4350094 http://www.medworm.com/index.php?rid=4350095&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216131%26dopt%3DAbstract Authors: Fletcher CA, Groom JR, Woehl B, Leung H, Mackay C, Mackay F B cell activating factor belonging to the TNF family (BAFF or BLyS) is a critical B cell survival factor essential for B cell maturation. BAFF transgenic (Tg) mice develop autoimmunity resembling Systemic Lupus Erythematosus (SLE) in a T cell-independent but toll-like receptor (TLR) signalling-dependent manner, requiring TLR-induced innate B cell-derived pro-inflammatory autoantibody deposition in the kidneys. Importantly, neutralizing BAFF in the clinic shows efficacy in patients with SLE, confirming its critical role in the progression of this disease in both humans and mouse models. The specific B cell types that produce autoantibodies in BAFF Tg mice are TLR-activated innate marginal zone (MZ) B cells and B1 cells... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4350095 Thu, 06 Jan 2011 00:00:00 +0100 4350095 http://www.medworm.com/index.php?rid=4350096&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21193288%26dopt%3DAbstract Authors: Aricha R, Mizrachi K, Fuchs S, Souroujon MC Suppressive regulatory T cells (Treg) and pathogenic T helper 17 (Th17) cells are two lymphocyte subsets with opposing activities in autoimmune diseases. The proinflammatory cytokine IL-6 is a potent factor in switching immune responses in vivo from the induction of Treg to pathogenic Th17 cells. We studied the Treg and Th17 cell compartments in experimental autoimmune myasthenia gravis (EAMG) and healthy control rats in order to assess whether the equilibrium between Treg and Th17 cells is perturbed in the disease. We found that Th17 cell-related genes are upregulated and Treg-related genes are downregulated in EAMG. The shift in favor of Th17 cells in EAMG could be reversed by antibodies to IL-6. Administration of anti-IL-6 antibod... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4350096 Tue, 28 Dec 2010 00:00:00 +0100 4350096 http://www.medworm.com/index.php?rid=4350097&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185149%26dopt%3DAbstract We report herein that such antibodies from patients, but not controls, produced a significant disruption of incomplete annexin A5 crystalline shield on phospholipid bilayer. In addition, the IgG fraction isolated from such patients significantly decreased the velocity of annexin A5 crystallization. Atomic force microscopy is a powerful tool to study the pathologic mechanisms of autoantibodies and the data herein reflect the potential of anti-annexin A5 antibodies that produce pathology in a number of varied but overlapping clinical conditions, including autoimmune thrombosis and antiphospholipid syndrome. PMID: 21185149 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4350097 Wed, 22 Dec 2010 00:00:00 +0100 4350097 http://www.medworm.com/index.php?rid=4222572&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21115235%26dopt%3DAbstract Authors: McKelvey KJ, Highton J, Hessian PA Toll-like receptors (TLRs) are key pattern recognition receptors during an immune response. With five isoforms of human TLR9 described, we hypothesised that differential expression of TLR9 isoforms in different cell types would result in variable contributions to the overall input from TLR9 during inflammation. We assessed the molecular expression of the TLR9 isoforms, TLR9-A, -C and -D. In normal peripheral blood mononuclear cells, B-lymphocytes express ∼100-fold more TLR9-A transcript than monocytes or T-lymphocytes, which predominantly express the TLR9-C transcript. Switches in isoform predominance accompany B-lymphocyte development. TLR9 protein expression in rheumatoid inflammatory lesions reflected the TLR9 isoform expression by immun... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4222572 Sat, 27 Nov 2010 00:00:00 +0100 4222572 http://www.medworm.com/index.php?rid=4203491&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21095100%26dopt%3DAbstract Authors: Wu GF, Shindler KS, Allenspach EJ, Stephen TL, Thomas HL, Mikesell RJ, Cross AH, Laufer TM Experimental autoimmune encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS), is dependent upon the activation and effector functions of autoreactive CD4 T cells. Multiple interactions between CD4 T cells and major histocompatibility class II (MHCII)+ antigen presenting cells (APCs) must occur in both the periphery and central nervous system (CNS) to elicit autoimmunity. The identity of the MHCII+ APCs involved throughout this process remains in question. We investigated which APC in the periphery and CNS mediates disease using transgenic mice with MHCII expression restricted to dendritic cells (DCs). MHCII expression restricted to DCs results in normal suscepti... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4203491 Sat, 20 Nov 2010 00:00:00 +0100 4203491 http://www.medworm.com/index.php?rid=4170566&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075597%26dopt%3DAbstract In this study, a modified version of the K/BxN model, the KRN-cell transfer model (KRN-CTM), was established to determine the contribution of Th17 cells in the development of chronic arthritis. The transfer of naive KRN T cells into B6.TCR.Cα(-/-)H-2(b/g7) T cell deficient mice induced arthritis by day 10 of transfer. Arthritis progressively developed for a period of up to 14 days following T cell transfer, thereafter the disease severity declined, but did not resolve. Both IL-17A and IFNγ were detected in the recovered T cells from the popliteal lymph nodes and ankles. The transfer of KRN Th17 polarized KRN CD4(+) T cells expressing IL-17A and IFNγ induced arthritis in all B6.TCR.Cα(-/-)H-2(b/g7) mice however the transfer of Th1 polarized KRN CD4(+) T cells expressing IFNγ alone ind... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4170566 Fri, 12 Nov 2010 00:00:00 +0100 4170566 http://www.medworm.com/index.php?rid=4170565&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075598%26dopt%3DAbstract In this study, we took advantages of the French DEFI database to investigate possible correlations between peripheral lymphocyte subpopulations and autoimmune clinical expression in CVID adult patients. In order to analyse homogeneous populations of patients with precise clinical phenotypes, we first focused on patients with autoimmune cytopenia because they represent prototypic autoantibody mediated diseases. In a secondary analysis, we have tested our conclusions including all "autoimmune" CVID patients. We describe one of the largest European studies with 311 CVID patients, including 55 patients with autoimmune cytopenia and 61 patients with clinical or serologic autoimmune expression, excluding autoimmune cytopenia. We clarify previous reports and we confirm a very significant correlat... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4170565 Fri, 12 Nov 2010 00:00:00 +0100 4170565 http://www.medworm.com/index.php?rid=4170567&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071175%26dopt%3DAbstract In conclusion, we identified novel candidate autoantibody markers for RA that can be detected in early and seronegative RA patients indicating the potential added value for RA diagnostics. PMID: 21071175 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4170567 Tue, 09 Nov 2010 00:00:00 +0100 4170567 http://www.medworm.com/index.php?rid=4140226&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21051205%26dopt%3DAbstract Authors: Meroni PL There has been considerable interest in the role of environmental factors and the induction of autoimmunity and the ways by which they facilitate loss of tolerance. Clearly both genetic and environmental factors are incriminated, as evidenced by the lack of concordance in identical twins and the relatively recent identification of the shared epitope in rheumatoid arthritis. In this issue a new syndrome called 'Asia'-autoimmune/auto-inflammatory syndrome induced by adjuvants has been proposed. It is an intriguing issue and one that is likely to be provocative and lead to further biologic and molecular investigations. PMID: 21051205 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4140226 Tue, 02 Nov 2010 00:00:00 +0100 4140226 http://www.medworm.com/index.php?rid=4140227&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21050716%26dopt%3DAbstract This study demonstrates that autoantigen-specific CD4(+) Treg clones with potential application as a cell therapy for autoimmune disease can be generated and expanded from human blood. PMID: 21050716 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4140227 Mon, 01 Nov 2010 00:00:00 +0100 4140227 http://www.medworm.com/index.php?rid=4140228&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035305%26dopt%3DAbstract Authors: Aricha R, Feferman T, Scott HS, Souroujon MC, Berrih-Aknin S, Fuchs S The autoimmune regulator (Aire) is involved in the prevention of autoimmunity by promoting thymic expression of tissue restricted antigens which leads to elimination of self-reactive T cells. We found that Aire knockout (KO) mice as well as mouse strains that are susceptible to experimental autoimmune myasthenia gravis (EAMG) have lower thymic expression of acetylcholine receptor (AChR- the main autoantigen in MG), compared to wild type (WT) mice and EAMG-resistant mouse strains, respectively. We demonstrated that Aire KO mice have a significant and reproducible lower frequency of CD4+Foxp3+ cells and a higher expression of Th17 markers in their thymus, compared to wild type (WT) mice. These findings led us ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4140228 Wed, 27 Oct 2010 00:00:00 +0100 4140228 http://www.medworm.com/index.php?rid=4108552&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970960%26dopt%3DAbstract Authors: Bayry J, Fournier EM, Maddur MS, Vani J, Wootla B, Sibéril S, Dimitrov JD, Lacroix-Desmazes S, Berdah M, Crabol Y, Oksenhendler E, Lévy Y, Mouthon L, Sautès-Fridman C, Hermine O, Kaveri SV Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or alleviating the severity of infections and autoimmune and inflammatory process in majority of CVID patients. Although the mechanisms of action of IVIg given as 'therapeutic high dose' in patients with autoimmune diseases are well studied, the underlying mechanisms of beneficial eff... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4108552 Wed, 20 Oct 2010 23:00:00 +0100 4108552 http://www.medworm.com/index.php?rid=4092215&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951001%26dopt%3DAbstract Authors: Thurner L, Müller A, Cérutti M, Martin T, Pasquali JL, Gross WL, Preuss KD, Pfreundschuh M, Voswinkel J Wegener's granulomatosis (WG) is a severe autoimmune disorder ranging from localized granulomatous disease to generalised anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A previous analysis of immunoglobulin heavy chain genes derived from tissue, i.e. Wegener's granuloma indicated selection and affinity maturation towards local antigen(s). The current study focused on determining the specificity of immunoglobulins from distinct B lymphocytes out of Wegener's granuloma. Four pairs of variable region immunoglobulin light and heavy chain genes, isolated before, were recombinantly expressed using the baculovirus/insect cell system. These immunoglobulins were... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4092215 Tue, 12 Oct 2010 23:00:00 +0100 4092215 http://www.medworm.com/index.php?rid=4066156&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20932718%26dopt%3DAbstract Authors: Martinic MM, Huber C, Coppieters K, Oldham JE, Gavin AL, von Herrath MG It is not fully understood how the expression level of autoantigens in beta cells impacts autoimmune diabetes (T1D) development. Earlier studies using ovalbumin and also insulin had shown that secreted antigens could enhance diabetes development through facilitated presentation by antigen presenting cells. Here we sought to determine how the expression level of a membrane bound, non-secreted or cross-presented neo-antigen, the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), would influence T1D. We found that an RIP-LCMV transgenic mouse line exhibiting higher levels of beta cell GP expression developed more severe diabetes after LCMV infection or transfer of high numbers of activated autore... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4066156 Mon, 04 Oct 2010 23:00:00 +0100 4066156 http://www.medworm.com/index.php?rid=4066155&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20932719%26dopt%3DAbstract Authors: Hintermann E, Bayer M, Pfeilschifter JM, Luster AD, Christen U Chemokines, such as CXCL10, promote hepatic inflammation in chronic or acute liver injury through recruitment of leukocytes to the liver parenchyma. The CXCL10 receptor CXCR3, which is expressed on a subset of leukocytes, plays an important part in Th1-dependent inflammatory responses. Here, we investigated the role of CXCL10 in chemically induced liver fibrosis. We used carbon tetrachloride (CCl(4)) to trigger chronic liver damage in wildtype C57BL/6 and CXCL10-deficient mice. Fibrosis severity was assessed by Sirius Red staining and intrahepatic leukocyte subsets were investigated by immunohistochemistry. We have further analyzed hepatic stellate cell (HSC) distribution and activation and investigated the effect ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4066155 Mon, 04 Oct 2010 23:00:00 +0100 4066155 http://www.medworm.com/index.php?rid=4066154&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20932720%26dopt%3DAbstract In conclusion, the PBC Screen is an appropriate first-line test for the diagnosis of PBC, including for patients negative for markers assessed using conventional methods. PMID: 20932720 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4066154 Mon, 04 Oct 2010 23:00:00 +0100 4066154 http://www.medworm.com/index.php?rid=4045996&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20884174%26dopt%3DAbstract Authors: Li M, Abraham NG, Vanella L, Zhang Y, Inaba M, Hosaka N, Hoshino SI, Shi M, Ambrosini YM, Gershwin ME, Ikehara S There is increasing evidence that both autoimmune and autoinflammatory mechanisms are involved in the development of not only type 1 diabetes mellitus (T1 DM), but also type 2 diabetes mellitus (T2 DM). Our laboratory has focused on this concept, and in earlier efforts replaced the bone marrow cells (BMCs) of leptin receptor-deficient (db/db) mice, an animal model of T2DM, with those of normal C57BL/6 (B6) mice by IBM-BMT. However, the outcome was poor due to incomplete recovery of T cell function. Therefore, we hypothesized that intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT + TT) could be used to treat T2 DM by normalizing the... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4045996 Mon, 27 Sep 2010 23:00:00 +0100 4045996 http://www.medworm.com/index.php?rid=4013774&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864316%26dopt%3DAbstract Authors: Iizuka M, Wakamatsu E, Tsuboi H, Nakamura Y, Hayashi T, Matsui M, Goto D, Ito S, Matsumoto I, Sumida T The aim of this study was to clarify the role of the immune response to muscarinic type 3 receptor (M3R) in the pathogenesis of Sjögren's syndrome (SS). M3R(-/-) mice were immunized with murine M3R peptides and their splenocytes were inoculated into Rag1(-/-) (M3R(-/-)→Rag1(-/-)) mice. M3R(-/-)→Rag1(-/-) mice had high serum levels of anti-M3R antibodies and low saliva volume. Histological examination showed marked infiltration of mononuclear cells in the salivary glands and immunohistochemistry demonstrated that the majority of these cells were CD4(+) T cells with a few B cells and several IFN-γ- and IL-17-producing cells. Apoptotic cells were present in the s... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4013774 Mon, 20 Sep 2010 23:00:00 +0100 4013774 http://www.medworm.com/index.php?rid=4013775&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20850948%26dopt%3DAbstract In this study, we used Non-obese diabetic (NOD) transgenic T cells engineered to express MHC class I-insulin peptide complexes linked to a T cell activation component (InsCD3-ζ), to target insulin-reactive CD8 T cells. We showed that activated, but not naïve, InsCD3-ζ CD8 T cells killed diabetogenic insulin-reactive CD8 target cells in vitro, inducing antigen-specific cell death mediated via both the release of perforin and the Fas-Fas ligand pathway. In vivo, InsCD3-ζ CD8 T cells migrated to the pancreatic lymph nodes of NOD mice after adoptive transfer. Concomitant with this, infiltration of CD8 T cells was also reduced in the pancreatic islets. Finally, in vivo, we showed that diabetes induced by adoptive transfer of insulin-reactive T cells was reduced following injection o... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=4013775 Wed, 15 Sep 2010 23:00:00 +0100 4013775 http://www.medworm.com/index.php?rid=3982327&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20843660%26dopt%3DAbstract Authors: Antiga E, Kretz CC, Klembt R, Massi D, Ruland V, Stumpf C, Baroni G, Hartmann M, Hartschuh W, Volpi W, Del Bianco E, Enk A, Fabbri P, Krammer PH, Caproni M, Kuhn A The purpose of this study was to characterize regulatory T cells (T(reg)) in skin lesions and peripheral blood from patients with dermatomyositis (DM) and to determine the serum levels of regulatory cytokines in the disease. In skin biopsy specimens from patients with DM, immunohistochemistry was performed for CD4(+), CD25(+), forkhead/winged helix transcription factor (FoxP3)(+), transforming growth factor (TGF)-β(+) and interleukin (IL)-10(+) cells. Additionally, we defined the number of T(reg) subpopulations in peripheral blood by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RO, CD9... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3982327 Sun, 12 Sep 2010 23:00:00 +0100 3982327 http://www.medworm.com/index.php?rid=3982326&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20843661%26dopt%3DAbstract Authors: Sundström M, Lejon K In non-obese diabetic (NOD) mice B cells are an absolute requirement for T1D development. NOD mice display various B cell related immune deviations when compared to normal mice such as an enhanced and prolonged immune response towards several antigens, including non-self immunoglobulins. We hypothesized that this trait contributes to diabetes pathogenesis, and investigated the genetic factor(s) governing the altered immune response. A (NODxC57BL/6)F(2) cohort (n = 214) were analyzed for its primary immune response against a BALB/c derived monoclonal antibody, and a genome wide linkage analysis was performed. Significant linkage to the Idd1/Idd24, Idd12 and Idd18.1 regions as well as to a proximal region (marker D2Mit367, 33.5 Mb) on chromosome ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3982326 Sun, 12 Sep 2010 23:00:00 +0100 3982326 http://www.medworm.com/index.php?rid=3973950&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20833509%26dopt%3DAbstract Authors: Baudino L, Changolkar LN, Pehrson JR, Izui S The endogenous retroviral envelope glycoprotein, gp70, implicated in murine lupus nephritis is secreted by hepatocytes, and its expression is largely regulated by the Sgp3 (serum gp70 production 3) locus derived from lupus-prone mice. Because of the localization of the macroH2A1 gene encoding macroH2A histone variants within the Sgp3 interval and of an up-regulated transcription of endogenous retroviral sequences in macroH2A1-deficient C57BL/6 (B6) mice, we investigated whether macroH2A1 is a candidate gene for Sgp3. macroH2A1-deficient B6 mice carrying the 129-derived Sgp3 locus, which was co-transferred with the 129 macroH2A1 mutant gene, displayed increased levels of serum gp70 and hepatic retroviral gp70 RNAs comparable to those... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3973950 Thu, 09 Sep 2010 23:00:00 +0100 3973950 http://www.medworm.com/index.php?rid=3973949&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20833510%26dopt%3DAbstract Authors: Lee TP, Tang SJ, Wu MF, Song YC, Yu CL, Sun KH Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characteristized by the presence of autoantibodies against double-stranded DNA (anti-dsDNA) in sera at high levels. Bacterial infections in SLE are associated with higher morbidity and mortality. Our goal was to observe the interaction between these 2 factors in the pathogenesis of lupus. We generated transgenic mice with monoclonal anti-dsDNA to investigate the development of lupus. By challenging the mice in vitro and in vivo with Toll-like receptor 4 (TLR4) ligand lipopolysaccharides (LPS), we were able to examine the role of bacterial infection in SLE. In our study, the transgenic mice with a secreted form of anti-dsDNA were found to have higher levels of a... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3973949 Thu, 09 Sep 2010 23:00:00 +0100 3973949 http://www.medworm.com/index.php?rid=3958249&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20822883%26dopt%3DAbstract Authors: Shao WH, Kuan AP, Wang C, Abraham V, Waldman MA, Vogelgesang A, Wittenburg G, Choudhury A, Tsao PY, Miwa T, Eisenberg RA, Cohen PL Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity. Splenic marginal zone B cells are important producers of autoantibodies, and are subject to stringent tolerance mechanisms to prevent autoimmunity. In this paper, we explore the role of the Mer tyrosine kinase (Mertk) in regulating autoreactive B cells. This receptor tyrosine kinase serves to bind apoptotic cells, to mediate their phagocytosis, and to regulate subsequent cytokine production. Mice lacking Mertk suffer from impaired apoptotic cell clearance and develop a lupus-like autoimmune syndrome. Here we show that such Mertk-KO mice ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3958249 Thu, 02 Sep 2010 23:00:00 +0100 3958249 http://www.medworm.com/index.php?rid=3958250&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20817405%26dopt%3DAbstract Authors: Mackay IR, Leskovsek NV, Rose NR The paradoxical relationship between immunodeficiency (under-responsiveness) and autoimmunity (over-responsiveness) affecting the immune system was debated at the Fourth AARDA Colloquium on cross-disciplinary issues in autoimmunity. Immunodeficiency disease and autoimmune disease, far from being mutually exclusive, share profound dysregulation of the immune system. Among the most keenly discussed issues were: i) the remarkably high number of molecularly identified primary immunodeficiencies with autoimmune expressions; ii) the homeostasis of immune function such that deficiency in any one given compartment can result in over activity in the same or another compartment; iii) whilst some immune deficiency states are essentially monogenic, each of... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3958250 Wed, 01 Sep 2010 23:00:00 +0100 3958250 http://www.medworm.com/index.php?rid=3903201&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20732843%26dopt%3DAbstract Authors: Fraussen J, Vrolix K, Martinez-Martinez P, Losen M, Meulemans E, De Baets MH, Stinissen P, Somers V We have developed a B cell immortalization method for low B cell numbers per well using simultaneous B cell stimulation by CpG2006 and B cell infection by Epstein-Barr virus (EBV), followed by an additional CpG2006 and interleukin-2 (IL-2) stimulus. Using this method, immunoglobulin G (IgG)-producing immortalized B cell lines were generated from peripheral blood IgG(+)CD22(+) B cells with an efficiency of up to 83%. Antibody can already be obtained from the culture supernatant after 3-4 weeks. Moreover, clonality analysis demonstrated monoclonality in 87% of the resulting immortalized B cell lines. Given the high immortalization efficiency and monoclonality rate, evidence is pro... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3903201 Thu, 26 Aug 2010 11:27:06 +0100 3903201 http://www.medworm.com/index.php?rid=3903202&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20727711%26dopt%3DAbstract Authors: Zuckerman NS, Hazanov H, Barak M, Edelman H, Hess S, Shcolnik H, Dunn-Walters D, Mehr R B cells have been found to play a critical role in the pathogenesis of several autoimmune (AI) diseases. A common feature amongst many AI diseases is the formation of ectopic germinal centers (GC) within the afflicted tissue or organ, in which activated B cells expand and undergo somatic hypermutation (SHM) and antigen-driven selection on their immunoglobulin variable region (IgV) genes. However, it is not yet clear whether these processes occurring in ectopic GCs are identical to those in normal GCs. The analysis of IgV mutations has aided in revealing many aspects concerning B cell expansion, mutation and selection in GC reactions. We have applied several mutation analysis methods, based ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3903202 Tue, 17 Aug 2010 23:00:00 +0100 3903202 http://www.medworm.com/index.php?rid=3856195&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20691570%26dopt%3DAbstract Authors: Santiuste I, Buelta L, Iglesias M, Genre F, Mazorra F, Izui S, Merino J, Merino R Genetic abnormalities predisposing to autoimmunity generally act in a cooperative manner affecting one or several mechanisms regulating immunological tolerance. In addition, many of these genetic abnormalities are also involved in the development of lymphoproliferative diseases. In the present study, we have determined the possible cooperation between deficiencies in members of the Cip/Kip family of cell cycle regulators (p21(WAF1/Cip1) or p27(kip1)) and the overexpression of human Bcl-2 in B lymphocytes in the induction of autoimmune and lymphoproliferative diseases in non-autoimmune C57BL/6 (B6) mice. Unlike single mutant mice, B6.p21(-/-) mice transgenic for human Bcl-2 in B cells developed a ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3856195 Tue, 03 Aug 2010 23:00:00 +0100 3856195 http://www.medworm.com/index.php?rid=3827472&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20685079%26dopt%3DAbstract This report enlightens disease-specific T-cell biomarkers and epitopes targeted in autoimmune adrenal deficiency. PMID: 20685079 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3827472 Sun, 01 Aug 2010 23:00:00 +0100 3827472 http://www.medworm.com/index.php?rid=3827471&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20685080%26dopt%3DAbstract Authors: Manoussakis MN, Kapsogeorgou EK Sjögren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3827471 Sun, 01 Aug 2010 23:00:00 +0100 3827471 http://www.medworm.com/index.php?rid=3827470&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20685081%26dopt%3DAbstract In conclusion, TLR-3 signaling pathway in the salivary epithelium appears to extend beyond the induction of innate immune responses and to involve the activation of programmed-cell death via anoikis. In the same context, the increased vulnerability of SS-SGEC to the injurious effect of TLR-3 ligation is likely associated with the intrinsic activation processes that apparently operate in the epithelia of SS patients, and a feature of key pathogenetic importance for the disorder. PMID: 20685081 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3827470 Sun, 01 Aug 2010 23:00:00 +0100 3827470 http://www.medworm.com/index.php?rid=3813475&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20673706%26dopt%3DAbstract Authors: Youinou P Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar's work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3813475 Wed, 28 Jul 2010 23:00:00 +0100 3813475 http://www.medworm.com/index.php?rid=3813474&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20674271%26dopt%3DAbstract Authors: Mavragani CP, Crow MK Sjogren's syndrome (SS), a chronic autoimmune systemic disease affecting middle aged women, is characterized by lymphocytic infiltration of the salivary and lachrymal glands resulting in dry eyes and dry mouth. Recent advances have revealed a major role for activation of the type I interferon (IFN) pathway in the pathogenesis of the syndrome, as evidenced by the increased circulating type I IFN activity and an IFN "signature" in peripheral blood mononuclear cells (PBMC) and minor salivary gland (MSG) biopsies from these patients. Polymorphisms in genes involved in the IFNalpha pathway, such as IRF5 and STAT4, have been found to be associated with disease susceptibility. While the initial triggers of the innate immune response in SS remain elusive, prelimi... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3813474 Wed, 28 Jul 2010 23:00:00 +0100 3813474 http://www.medworm.com/index.php?rid=3813476&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20673622%26dopt%3DAbstract In this study we demonstrate that the anti-Ro/SSA autoantibodies (Abs) stimulate the production of pro-inflammatory cytokines IL-6 and IL-8 by human healthy salivary gland epithelial cells (healthy SGEC). The secretion of these cytokines is due to amphiregulin (AREG) that is overexpressed in healthy SGEC treated with anti-Ro/SSA Abs and in Sjögren's syndrome. We have discovered that the up-regulation of AREG occurs through TNF-alpha produced following anti-Ro/SSA Abs treatment. The gene silencing technique was used to study the AREG-TNF-alpha-IL-6/IL-8 secretion pathway, demonstrating that: (i) TNF-alpha gene silencing provokes a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated healthy SGEC; (ii) AREG gene silencing has a potent... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3813476 Mon, 26 Jul 2010 23:00:00 +0100 3813476 http://www.medworm.com/index.php?rid=3795742&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655705%26dopt%3DAbstract Authors: Passam FH, Qi JC, Tanaka K, Matthaei KI, Krilis SA Beta 2 glycoprotein I (beta2GPI) is the major auto antigen in the antiphospholipid syndrome but also interacts with fibrinolytic and angiogenic proteins. The aim of this study was to examine the angiogenic potential of beta2GPI in vivo in beta2GPI deficient mice utilizing angiogenic assays. beta2GPI deficient mice show increased microvessel formation in comparison to beta2GPI replete controls when injected with growth factor free-matrigel implants. However, microvessel formation in matrigel plugs of beta2GPI deficient mice was less than in beta2GPI replete mice when basic fibroblast growth factor (bFGF) was included in the matrigel. Hemoglobin content was higher in vascular endothelial growth factor (VEGF) containing-matrigel ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3795742 Wed, 21 Jul 2010 23:00:00 +0100 3795742 http://www.medworm.com/index.php?rid=3795741&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655706%26dopt%3DAbstract Authors: Miyagawa F, Gutermuth J, Zhang H, Katz SI A major emphasis of our studies has been on developing a better understanding of how and why the skin serves as a target for immune reactions as well as how the skin evades becoming a target for destruction. For these studies we developed transgenic mice that express a membrane-tethered form of a model self antigen, chicken ovalbumin (mOVA), under the control of a keratin 14 (K14) promoter. K14-mOVA transgenic mice that express OVA mRNA and protein in the epithelia have been assessed for their immune responsiveness to OVA and are being used as targets for T cells obtained from OT-1 transgenic mice whose CD8+ T cells carry a Valpha2/Vbeta5-transgenic T cell receptor with specificity for the OVA(257-264)-peptides (OVAp) in association wi... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3795741 Wed, 21 Jul 2010 23:00:00 +0100 3795741 http://www.medworm.com/index.php?rid=3795745&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20650610%26dopt%3DAbstract Authors: Tsuda M, Torgerson TR, Selmi C, Gambineri E, Carneiro-Sampaio M, Mannurita SC, Leung PS, Norman GL, Gershwin ME IPEX syndrome is a congenital disorder of immune regulation caused by mutations in the FOXP3 gene, which is required for the suppressive function of naturally arising CD4 + CD25 + regulatory T cells. In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantibodies associated with a broad range of autoimmune disorders. We note that 75% of patients (9/12) had 1 or more autoantibodies, an incidence far above the cumulative rate observed in the general population. The range of autoantibodies differed between patients and there was no predominant autoantibody or pattern of autoantibodies present in this cohort. S... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3795745 Tue, 20 Jul 2010 23:00:00 +0100 3795745 http://www.medworm.com/index.php?rid=3795744&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20650611%26dopt%3DAbstract Authors: Wiik AS, Høier-Madsen M, Forslid J, Charles P, Meyrowitsch J The choice of terms used to describe indirect immunofluorescence (IIF) staining patterns of autoantibodies binding to HEp-2 cells is at present quite varied and disordered because no accurate consensus on names and descriptions exist. The aim of our study was to propose a logical and ordered IIF classification taxonomy based on 29 different selected IIF patterns. In a preliminary project carried out at Statens Serum Institut it was first shown by use of a software programme named DOORS developed by Percepton Ltd, that reading of digitized images of HEp-2 patterns on an LCD monitor could be used instead of traditional microscopy. Digitized images of HEp-2 patterns were then used in the EU supported project named CA... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3795744 Tue, 20 Jul 2010 23:00:00 +0100 3795744 http://www.medworm.com/index.php?rid=3795743&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655174%26dopt%3DAbstract Authors: Roguedas AM, Pers JO, Lemasson G, Devauchelle V, Tobón GJ, Saraux A, Misery L, Youinou P There is a crucial need for reliable diagnostic criteria for SS. Our objective was to evaluate the frequency of xerosis in patients with primary Sjögren's syndrome (SS), and compare histopathology of cutaneous sweat glands and labial salivary glands (LSGs), with respect to their contribution to the diagnosis. Twenty-two patients with primary SS and 22 matched normal volunteers were invited to rate their skin dryness on a visual analog scale. The skin was dryer (58.3 +/- 10.1 versus 38.9 +/- 7.6, P < 0.01), and xerosis more frequent (9 of 22 versus 2 of 22, P < 0.02) in the patients than in the controls. The axilla skin was chosen for a 6-mm punch biopsy. Lymphocytic infiltratio... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3795743 Tue, 20 Jul 2010 23:00:00 +0100 3795743 http://www.medworm.com/index.php?rid=3780669&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20643529%26dopt%3DAbstract Authors: Routsias JG, Tzioufas AG A common serologic finding in systemic autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Although their pathogenesis is not fully understood, autoantibodies are important tools for establishing diagnosis, classification and prognosis of autoimmune diseases. In Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome (SS) autoantibodies mainly target multicomponent ribonucleoprotein complex Ro/La RNP. The last years, the main characteristics, the clinical significance of the anti-Ro/SSA and anti-La/SSB autoantibodies, their biologic function, as well as their B-cell antigenic determinants (epitopes) have been addressed. More specifically, the structural characteristics and clinical associations of epitopes alo... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3780669 Fri, 16 Jul 2010 23:00:00 +0100 3780669 http://www.medworm.com/index.php?rid=3780668&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20643530%26dopt%3DAbstract Authors: Kapsogeorgou EK, Manoussakis MN Costimulatory molecules are cell-surface glycoproteins that can direct, modulate and fine tune immune responses. B7-2(CD86) costimulatory molecules are considered as major regulators of T cell responses, acting by appropriate interactions with the stimulatory CD28 or inhibitory CTLA-4 receptors found on T cells. Although their expression is thought to be restricted in lymphoid cells, evidence raised during the last decade show their expression in other types of cells, including human non-neoplastic salivary gland epithelial cells (SGEC). The expression of B7-2 molecules by SGECs requires special attention, due to their unique expression pattern and distinctive binding properties. Thus, SGECs express three B7-2 alternate transcripts that encode t... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3780668 Fri, 16 Jul 2010 23:00:00 +0100 3780668 http://www.medworm.com/index.php?rid=3767623&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638238%26dopt%3DAbstract Authors: Vlachoyiannopoulos PG, Routsias JG Antiphospholipid antibody syndrome (APS) is an autoimmune thrombophilia mediated by autoantibodies directed against phospholipid-binding plasma proteins, mainly beta2 Glycoprotein I (beta2GPI)-a plasma apolipoprotein and prothrombin (PT). A subgroup of these antibodies termed "Lupus Anticoagulant" (LA) elongate in vitro the clotting times, this elongation not corrected by adding normal plasma in the detection system. The exact mechanism by which these autoantibodies induce thrombosis is not well understood. Resistance to natural anticoagulants such as protein C, impaired fibrinolysis, activation of endothelial cells to a pro-coagulant phenotype and activation of platelets, are among the mechanisms partially supported by experimental evidence.... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3767623 Wed, 14 Jul 2010 23:00:00 +0100 3767623 http://www.medworm.com/index.php?rid=3767622&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638239%26dopt%3DAbstract In conclusion, these data identify the CD8 Treg subset as a regulatory T cell subpopulation altered in patients with PBC. PMID: 20638239 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3767622 Wed, 14 Jul 2010 23:00:00 +0100 3767622 http://www.medworm.com/index.php?rid=3767621&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638240%26dopt%3DAbstract Authors: Scheinecker C, Bonelli M, Smolen JS The development of autoimmune diseases is characterized by the breakdown of mechanism(s) that are responsible for maintaining immunological tolerance against self-structures in the periphery. Several aberrations of immune cells have been described so far. Most recently quantitative and/or qualitative defects of T cells with the capacity to suppress or regulate the proliferation of effector T cells in vitro - subsequently termed regulatory T cells (Treg) - have been suggested to substantially contribute to the imbalance of peripheral tolerance and trigger the outbreak of autoimmune reactions. The aim of this article is to summarize current knowledge about pathomechanisms that are involved in the development of autoimmunity with a special emph... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3767621 Wed, 14 Jul 2010 23:00:00 +0100 3767621 http://www.medworm.com/index.php?rid=3767620&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638241%26dopt%3DAbstract Authors: Kontaki E, Boumpas DT Historically, the involvement of complement - an integral part of the innate immune response- in the pathogenesis of lupus was recognized early. Emphasis shifted quickly however to the specific immunity with scientists concentrating on the adaptive immune response (autoantigens, autoreactive T cells and autoantibodies). Similarly, the detection of interferon alpha (IFNalpha), another key mediator of innate immunity, in the sera of active lupus patients by Hooks and Moutsopoulos in 1979 was poorly understood and thus ignored for many years. More recently however, the realization that a) endogenous ligands ("stressors") derived from a "stressed" host can be potent inducers of inflammatory mediators, and b) a cross-talk exists between the innate and the spec... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3767620 Wed, 14 Jul 2010 23:00:00 +0100 3767620 http://www.medworm.com/index.php?rid=3767619&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638242%26dopt%3DAbstract In this study we assessed the impact of immunosuppression on inflammatory insulitis in NOD mice, and the effect of radiation on immunomodulation mediated by adoptive transfer of various cell subsets. Sublethal radiation of NOD females at the age of 14 weeks (onset of hyperglycemia) delayed the onset of hyperglycemia, however two thirds of the mice became diabetic. Adoptive transfer of splenocytes into irradiated NON and NOD mice precipitated disease onset despite increased contents of CD25(+)FoxP3(+) T cells in the pancreas and regional lymphatics. Similar phenotypic changes were observed when CD25(+) T cells were infused after radiation, which also delayed disease onset without affecting its incidence. Importantly, irradiation increased the susceptibility to diabetes in NOD and NON mice (... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3767619 Wed, 14 Jul 2010 23:00:00 +0100 3767619 http://www.medworm.com/index.php?rid=3767618&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638243%26dopt%3DAbstract Authors: Juran BD, Lazaridis KN Despite recent progress, the pathogenic mechanisms governing PBC development, treatment response and outcome remain unknown. This deficiency is in large part due to the complex nature of PBC, wherein various environmental factors may be capable of prompting disease, but only in the context of underlying genetic susceptibility. Identification of genomic loci containing these heritable risk factors has been slowed by the rarity and late onset of PBC, which has made difficult the collection of sufficient numbers of patients and family members for meaningful genetic analyses. Advancements in our ability to catalog the genetic variation in large numbers of individuals at a genome-wide scale, coupled with unprecedented efforts to recruit PBC patients for genet... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3767618 Wed, 14 Jul 2010 23:00:00 +0100 3767618 http://www.medworm.com/index.php?rid=3751068&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20619604%26dopt%3DAbstract Authors: Baudino L, Yoshinobu K, Dunand-Sauthier I, Evans LH, Izui S The endogenous retroviral envelope glycoprotein, gp70, implicated in murine systemic lupus erythematosus (SLE), has been considered to be a product of xenotropic, polytropic (PT) and modified PT (mPT) endogenous retroviruses. It is secreted by hepatocytes like an acute phase protein, but its response is under a genetic control. Given critical roles of TLR7 and TLR9 in the pathogenesis of SLE, we assessed their contribution to the acute phase expression of serum gp70, and defined a pivotal role of the Sgp3 (serum gp70 production 3) and Sgp4 loci in this response. Our results demonstrated that serum levels of gp70 were up-regulated in lupus-prone NZB mice injected with TLR7 or TLR9 agonist at levels comparable to those ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3751068 Tue, 06 Jul 2010 23:00:00 +0100 3751068 http://www.medworm.com/index.php?rid=3711403&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20580204%26dopt%3DAbstract Authors: Volovitz I, Marmor Y, Mor F, Flügel A, Odoardi F, Eisenbach L, Cohen IR T cell vaccination (TCV) with irradiated encephalitogenic T cells induces resistance to EAE. However, the fate of the encephalitogenic T cells in vivo following TCV has yet to be studied. Here we used anti-MBP encephalitogenic T cells that were transduced to express GFP to study the effects of TCV on these cells. In naïve rats or in control-vaccinated (Ova-GFP) rats injected i.v. with GFP-labeled effector cells, high numbers of effector T cells were found along with macrophages, CD8 T cells and Non-GFP CD4 cells in the spleens, parathymic lymph nodes (PTLN) and spinal cords. In contrast, the recipients that had been treated with TCV (anti-MBP T-cell lines) showed few if any GFP-labeled effector T cel... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3711403 Wed, 23 Jun 2010 23:00:00 +0100 3711403 http://www.medworm.com/index.php?rid=3711404&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20579844%26dopt%3DAbstract Authors: Zhang AH, Li X, Onabajo OO, Su Y, Skupsky J, Thomas JW, Scott DW Antigen-specific tolerance induction using autologous B-cell gene therapy is a potential treatment to eliminate undesirable immune responses. For example, we have shown that experimental autoimmune encephalomyelitis (EAE) and type 1 diabetes in NOD mice can be ameliorated using antigen-Ig fusion protein transduced B cells. However, it is well established that auto-reactive antigen-specific B cells are activated in many autoimmune diseases and can contribute to pathogenesis. While syngeneic B cells from immunized or autoimmune mice can serve as tolerogenic antigen-presenting cells (APC), this observation begs the question of whether the antigen-specific B cells per se can be transduced as tolerogenic APC. To test ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3711404 Tue, 22 Jun 2010 23:00:00 +0100 3711404 http://www.medworm.com/index.php?rid=3590936&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20488663%26dopt%3DAbstract In this study, we found that B cells from PanLN of 3-4-week-old female NOD mice expressed high levels of alpha(4) integrin and LFA-1 and intermediate levels of beta(7) integrin; half of B cells were L-selectin(high). In short-term in vivo lymphocyte migration assays, B cells migrated from the bloodstream into PanLN more efficiently than into peripheral LNs. Moreover, antibodies to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and alpha(4)beta(7) integrin inhibited >90% of B cell migration into PanLN. In contrast, antibodies to peripheral node addressin, L-selectin or LFA-1 partially inhibited B cell migration into PanLN. Furthermore, one intraperitoneal injection of anti-MAdCAM-1 antibody into 3-week-old NOD mice significantly inhibited entry of B cells into PanLN for at least 2... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3590936 Mon, 17 May 2010 23:00:00 +0100 3590936 http://www.medworm.com/index.php?rid=3590935&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20488664%26dopt%3DAbstract In this study, we report for the first time that endothelial cells overexpressing IFI16 undergo apoptosis via the activation of caspase 2 and caspase 3, and that a positive feedback loop appears to link these two caspases. The relevance of IFI16-mediated apoptosis is highlighted by the observation that IFI16 knock down by RNA interference in endothelial cells inhibits the activation of both caspase 2 and caspase 3 by IFN-beta priming and synthetic double-stranded RNA treatment. Expression of a dominant-negative mutant of IKK2 kinase or treatment with AS602868, an inhibitor of IKK2 activity, results in a strong reduction of NF-kB activation along with absence of caspase 2 and caspase 3 activation and apoptosis induction. Collectively, our findings provide new insights into the role of IFI16... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3590935 Mon, 17 May 2010 23:00:00 +0100 3590935 http://www.medworm.com/index.php?rid=3534333&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20434883%26dopt%3DAbstract In conclusion, oral treatment with IIIM1 ameliorates EAE symptoms via stimulation of Tregs to proliferate and produce RA1 which reduces EAE symptoms. RA1 might be involved in the relatively low prevalence of MS in Japan and other Japanese rice-eating populations. PMID: 20434883 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3534333 Wed, 28 Apr 2010 23:00:00 +0100 3534333 http://www.medworm.com/index.php?rid=3468504&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20382503%26dopt%3DAbstract Authors: Lloyd ML, Papadimitriou JM, O'Leary S, Robertson SA, Shellam GR Antibodies reactive with the ovarian glycoprotein zona pellucida (ZP) have been linked with human female infertility. Anti-fertility vaccines that target ZP antigens have been utilized to restrict pest animal populations and their efficacy is associated with ovary-specific antibody induction. However, the necessity for zona pellucida-specific antibody in mediating infertility has not been examined in vivo. A recombinant mouse cytomegalovirus vaccine encoding murine zona pellucida 3 that induces rapid and complete infertility in BALB/c mice has been produced. The onset of infertility is temporally related to the presence of antibody sequestered into ovarian follicles and binding to the ZP of infected mice and the l... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3468504 Thu, 08 Apr 2010 23:00:00 +0100 3468504 http://www.medworm.com/index.php?rid=3435375&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20356713%26dopt%3DAbstract Authors: Elo LL, Mykkänen J, Nikula T, Järvenpää H, Simell S, Aittokallio T, Hyöty H, Ilonen J, Veijola R, Simell T, Knip M, Simell O, Lahesmaa R Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing pancreatic beta cells in the islets of Langerhans. Although defects in various T cell subsets have been linked to the disease pathogenesis, mechanisms initiating or enhancing the autoimmunity in prediabetes remain poorly understood. To unravel genes and molecular pathways affected by the diabetes-associated autoimmunity, we investigated transcriptomic profiles of prospective whole-blood samples from children who have developed T1D-associated autoantibodies and eventually clinical T1D. Gene-level investigation of the data showed systematic d... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3435375 Sun, 28 Mar 2010 23:00:00 +0100 3435375 http://www.medworm.com/index.php?rid=3392854&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20303712%26dopt%3DAbstract Authors: Menconi F, Huber A, Osman R, Concepcion E, Jacobson EM, Stefan M, David CS, Tomer Y An HLA-DR variant containing Arginine at position 74 of the DRbeta1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's thyroiditis (HT), while Glutamine at position DRbeta1-74 is protective. We hypothesized that the DRbeta1-Arg74 variant is able to present pathogenic thyroglobulin (Tg) peptides to T-cells more efficiently, thereby triggering thyroid autoimmunity. Indeed, we have previously identified 4 human Tg (hTg) peptides that bind specifically to DRbeta1-Arg74 with much weaker binding to the protective variant DRbeta1-Gln74. The aim of our study was to examine in vivo whether an hTg peptide that binds strongly and speci... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3392854 Thu, 18 Mar 2010 00:00:00 +0100 3392854 http://www.medworm.com/index.php?rid=3363009&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20223637%26dopt%3DAbstract We report that the expression and activity of the transcription factor RFX1 are decreased in SLE CD4(+) T cells. We demonstrate that RFX1 affects DNA methylation and histone acetylation in CD4(+) T cells by recruiting the co-repressors DNMT1 and HDAC1 to the CD11a and CD70 promoters, and thereby represses their expression. Reducing RFX1 in CD4(+) T cells is sufficient to cause lupus-like T and B cell hyperactivity, whereas overexpressing RFX1 suppresses T cell reactivity. These findings reveal a crucial role for RFX1 in regulating the epigenetic status of T cells, and demonstrate that autoimmune responses in SLE are due in part to RFX1 downregulation. PMID: 20223637 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3363009 Tue, 09 Mar 2010 00:00:00 +0100 3363009 http://www.medworm.com/index.php?rid=3363008&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20223638%26dopt%3DAbstract CONCLUSION: Our study implies varying degrees of risk for familial autoimmunity among subtypes of SSc and provides further support for common genetic and potentially environmental factors leading to SSc and SLE. PMID: 20223638 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3363008 Tue, 09 Mar 2010 00:00:00 +0100 3363008 http://www.medworm.com/index.php?rid=3303402&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20172692%26dopt%3DAbstract Authors: York NR, Mendoza JP, Ortega SB, Benagh A, Tyler AF, Firan M, Karandikar NJ Immune-based self-recognition and failure to modulate this response are believed to contribute to the debilitating autoimmune pathology observed in multiple sclerosis (MS). Studies from its murine model, experimental autoimmune encephalomyelitis (EAE), have shown that neuroantigen-specific CD4+T cells are capable of inducing disease, while their immune sibling, the CD8+T cells, have largely been ignored. To understand their role in autoimmune demyelination, we first confirmed that, similar to our observations in human MS, there is robust induction of neuroantigen-reactive CD8+T cells in several models, including MOG(35-55)/CFA-induced EAE. However, MOG(35-55)-specific CD8+T-cells, when purified, were un... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3303402 Fri, 19 Feb 2010 00:00:00 +0100 3303402 http://www.medworm.com/index.php?rid=3270175&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20149596%26dopt%3DAbstract Authors: Santiago-Raber ML, Amano H, Amano E, Fossati-Jimack L, Swee LK, Rolink A, Izui S The development of systemic lupus is accelerated by the Yaa (Y-linked autoimmune acceleration) mutation, which is the consequence of a translocation of the telomeric end containing the Tlr7 gene from the X chromosome onto the Y chromosome. However, the loss of marginal zone (MZ) B cells, one of the Yaa-linked cellular abnormalities, has previously been shown to be unrelated to the Tlr7 gene duplication, and the present study therefore aimed to investigate the mechanism responsible for MZ B-cell loss. Analyses of Yaa and non-Yaa C57BL/6 male mice expressing an MD4 anti-HEL IgM transgene or those deficient in fms-like tyrosine kinase 3 ligand (FL) revealed that the proportion of MZ B cells in these ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3270175 Tue, 09 Feb 2010 00:00:00 +0100 3270175 http://www.medworm.com/index.php?rid=3255539&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20138735%26dopt%3DAbstract Authors: Dugas V, Beauchamp C, Chabot-Roy G, Hillhouse EE, Lesage S CD47 and signal regulatory protein (SIRP) interactions have been proposed to take part in autoimmune disease susceptibility. Importantly, a recent genome-wide association study for type 1 diabetes susceptibility highlighted the association of the 20p13 region comprising the SIRP cluster, where some of the SIRP proteins encode functional ligands to CD47. Using a TCR transgenic mouse model at the brink of autoimmune disease, we demonstrate that CD47-deficiency is sufficient to break the immune tolerance and provoke the onset of autoimmune diabetes. Interestingly, CD47-deficient mice show a severe reduction in the number of mature CD4(-)CD8(-) T cells, and passive transfer of these CD4(-)CD8(-) T cells is sufficient to re... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3255539 Fri, 05 Feb 2010 00:00:00 +0100 3255539 http://www.medworm.com/index.php?rid=3205411&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20096538%26dopt%3DAbstract Authors: Powell JJ, Faria N, Thomas-McKay E, Pele LC Humans have evolved with oral exposure to dietary microparticles and nanoparticles as a normal occurrence but the ever-growing exploitation of nanotechnology is likely to increase exposure further, both qualitatively and quantitatively. Moreover, unlike the situation with respirable particles, relatively little is known about gastrointestinal intake and handling of nanoparticles. With a long term interest in gut exposure and responses to dietary microparticles, our group is now applying its expertise to nanoparticles in the gastrointestinal tract. Here we aim to address (i) the current challenges associated with the characterisation of particle-host or particle-cell interactions, (ii) the origin and mechanisms of uptake of particles ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3205411 Wed, 20 Jan 2010 00:00:00 +0100 3205411 http://www.medworm.com/index.php?rid=3189716&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080387%26dopt%3DAbstract Authors: Tobón GJ, Youinou P, Saraux A Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20-50 cases per 100,000 population and the prevalence at 0.5-1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic fac... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3189716 Fri, 15 Jan 2010 00:00:00 +0100 3189716 http://www.medworm.com/index.php?rid=3189715&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080388%26dopt%3DAbstract This study reveals a novel specificity for gammadelta TCRs, and raises the possibility that gammadelta T cells become involved in islet-specific autoimmunity. PMID: 20080388 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity) Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3189715 Fri, 15 Jan 2010 00:00:00 +0100 3189715 http://www.medworm.com/index.php?rid=3189717&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20079608%26dopt%3DAbstract Authors: Maciejewska-Rodrigues H, Karouzakis E, Strietholt S, Hemmatazad H, Neidhart M, Ospelt C, Gay RE, Michel BA, Pap T, Gay S, Jüngel A The aggressive phenotype of RA synovial fibroblasts (RASF) is characterised by the increased expression of matrix metalloproteinase (MMP)-1 as well as the small ubiquitin like modifier (SUMO)-1 and decreased expression of SUMO-specific protease SENP1. Since we showed an increased activity of acetyltransferases in this autoimmune disease, we wanted to analyze whether this affects the expression of MMP-1 and can be reversed by the reconstitution of SENP1. In RASF, the acetylation of histone H4 was significantly increased in the distal region of the MMP-1 promoter by 274 +/- 36% compared to OASF. Most interestingly, overexpression of SENP1 in RAS... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3189717 Wed, 13 Jan 2010 00:00:00 +0100 3189717 http://www.medworm.com/index.php?rid=3164777&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061119%26dopt%3DAbstract Authors: Chamberlain JL, Pittock SJ, Oprescu AM, Dege C, Apiwattanakul M, Kryzer TJ, Lennon VA Peripherin-IgG has been reported a pertinent autoantibody in non-obese type 1 diabetic (NOD) mice. However, it has not previously been recognized in any human disease. In blinded evaluation of serum for markers of neurological autoimmunity in a high-volume diagnostic laboratory, we incidentally identified 26 patients (61% female) with an IgG that bound selectively to neural elements in enteric ganglia, sympathetic nerve trunks and discrete nerve tracts in mid-brain and hind-brain. The target antigen was identified as peripherin, a 55kDa - type III intermediate filament protein. Review of clinical histories revealed that 54% of seropositive patients had dysautonomia (predominantly gastrointest... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3164777 Fri, 08 Jan 2010 00:00:00 +0100 3164777 http://www.medworm.com/index.php?rid=3164776&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061120%26dopt%3DAbstract Authors: Behrens M, Trejo T, Luthra H, Griffiths M, David CS, Taneja V HLA class II allele DRB1*0401 is associated with predisposition to Rheumatoid Arthritis in humans as well as collagen-induced arthritis in mice. Predominantly females develop arthritis in humans and DR4 transgenic mice; however the mechanism of sex-bias is still unknown. We have investigated the molecular basis by which DR4 is associated with sex-bias of arthritis. Here we show that differential antigen-specific immune mechanisms in DR4 male and female mice lead to increased susceptibility in female mice. B cells are hyperactive and present DR-restricted peptides robustly in females compared to males. Antigen-specific response showed that females produced B cell modulating cytokines like IL-13 while males produced I... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3164776 Fri, 08 Jan 2010 00:00:00 +0100 3164776 http://www.medworm.com/index.php?rid=3156728&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20053532%26dopt%3DAbstract Authors: Brooks WH, Le Dantec C, Pers JO, Youinou P, Renaudineau Y Advances in genetics, such as sequencing of the human genome, have contributed to identification of susceptible genetic patterns in autoimmune diseases (AID). However, genetics is only one aspect of the diseases that does not reflect the influence of environment, sex or aging. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, showing differences between AID patients and healthy controls but also showing how one disease differs from another. With regards to epigenetic abnormalit... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3156728 Mon, 04 Jan 2010 00:00:00 +0100 3156728 http://www.medworm.com/index.php?rid=3136041&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20042314%26dopt%3DAbstract Authors: Arnson Y, Shoenfeld Y, Amital H Smoking is a central factor in many pathological conditions. Its role in neoplasm, lung and cardiovascular diseases has been well established for years. However it is less acknowledged the cigarette smoking affects both the innate and adoptive immune arms. Cigarette smoke was shown to augment the production of numerous pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6, IL-8 GM-CSF and to decrease the levels of anti-inflammatory cytokines such as IL-10. Tobacco smoke via multiple mechanisms leads to elevated IgE concentrations and to the subsequent development of atopic diseases and asthma. Cigarette smoke has also been shown activate in many ways macrophage and dendritic cell activity. While it is better evident how cigarette smoke evokes... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3136041 Mon, 28 Dec 2009 00:00:00 +0100 3136041 http://www.medworm.com/index.php?rid=3125815&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20036105%26dopt%3DAbstract Authors: Invernizzi P Autoimmune liver diseases are characterized by immune mediated injury of bile ducts or hepatocytes, thus including cholangiopathies such as primary biliary cirrhosis, primary sclerosing cholangitis, and immunoglobulin G4-associated cholangitis, and autoimmune hepatitis. Although the liver was one of the earliest recognized sites of autoimmune aggression, the aetiology of autoimmune liver diseases remains largely obscure and their clinical management still difficult. Since an ever increasing applicability of immunology to a wide variety of chronic diseases, basic and clinical knowledge on autoimmune liver diseases grow rapidly in the last few years. This review will mainly focus on the available geoepidemiology data of these disorders, but it will deal also on thei... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3125815 Wed, 23 Dec 2009 00:00:00 +0100 3125815 http://www.medworm.com/index.php?rid=3125814&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20036106%26dopt%3DAbstract Authors: Takada Y, Ono Y, Sagusa J, Mitsiades C, Mitsiades N, Tsai J, He Y, Maningding E, Coleman A, Ramirez-Maverakis D, Rodriquez R, Takada Y, Maverakis E The C-terminal domain of the fibrinogen gamma chain (gammaC) has been shown to bind to the integrins alphaIIbbeta3, alphaMbeta2 and alphaVbeta3. It has also been reported that a peptide derived from the alphaMbeta2-binding site of gammaC can suppress an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Here we have truncated gammaC at position 399 to remove the prothrombotic alphaIIbbeta3-binding site. We show that this truncated version of gammaC, termed gammaC399tr, can bind to activated T cells. In addition, T cells incubated with gammaC399tr secreted less IFN-gamma when stimulated with antigen... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3125814 Wed, 23 Dec 2009 00:00:00 +0100 3125814 http://www.medworm.com/index.php?rid=3123562&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20034760%26dopt%3DAbstract Authors: Chandran V, Raychaudhuri SP Psoriasis and Psoriatic Arthritis (PsA) are chronic inflammatory diseases that have a major impact on health. The prevalence and incidence estimates of these two closely related diseases show ethnic and geographic variations, being generally more common in the colder north than in the tropics. In Europe the prevalence of psoriasis varies anywhere from 0.6 to 6.5%. In the USA, the estimated prevalence of diagnosed psoriasis is 3.15%. The prevalence in Africa varies depending on geographic location, being lowest in West Africa. Psoriasis is less prevalent in China and Japan than in Europe, and is entirely absent in natives of the Andean region of South America. There are fewer reports on the incidence of psoriasis, but a recent study from Rochester, U... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3123562 Tue, 22 Dec 2009 00:00:00 +0100 3123562 http://www.medworm.com/index.php?rid=3123561&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20034761%26dopt%3DAbstract Authors: Shapira Y, Agmon-Levin N, Shoenfeld Y Autoimmune diseases cumulatively affect 5-10% of the industrial world population and are a significant cause of morbidity and mortality. In recent decades rates are rising worldwide, and autoimmunity can no longer be associated solely with the more developed "Western" countries. Geoepidemiology of autoimmune diseases portrays the burden of these illnesses across various regions and ethnic populations. Furthermore, Geoepidemiology may yield important clues to the genetic and triggering environmental mechanisms of autoimmunity. In this review we compiled and discuss in depth abundant geoepidemiological data pertaining to four major autoimmune conditions, namely type-1 diabetes mellitus, multiple sclerosis, autoimmune thyroid disease, and inf... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3123561 Tue, 22 Dec 2009 00:00:00 +0100 3123561 http://www.medworm.com/index.php?rid=3120750&cid=s_33858_3_f&fid=33858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20031371%26dopt%3DAbstract Authors: Borchers AT, Naguwa SM, Keen CL, Gershwin ME There are multiple epidemiological studies that document the potential adverse affects of autoimmunity on nearly every aspect of reproduction, even in the absence of clinically manifest autoimmune disease. Two decades ago, it was suggested that women with autoimmune diseases avoid pregnancy due to inordinate risks to the mother and the child. In contrast, newer epidemiological data demonstrated that advances in the treatment of autoimmune diseases and the management of pregnant women with these diseases have similarly improved the prognosis for mother and child. In particular, if pregnancy is planned during periods of inactive or stable disease, the result often is giving birth to healthy full-term babies without increased risks of ... Journal of Autoimmunity journals http://www.medworm.com/rss/comments.php?id=3120750 Mon, 21 Dec 2009 00:00:00 +0100 3120750