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A comprehensive evaluation of serum autoantibodies in primary biliary cirrhosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In primary biliary cirrhosis (PBC) serum markers other than anti-mitochondrial antibodies (AMA) are promising in terms of disease severity and comorbidities, as well represented by anti-nuclear antibodies (ANA). The aim of the present study was thus to evaluate the prevalence and clinical significance of a large profile of serum autoantibodies in PBC sera. We utilized 69 sera from European patients with PBC (including 20 AMA-negative) and 297 sera from geographically and sex-matched healthy controls. All sera were tested for the presence of ANA and autoantibodies associated with thrombophilia, vasculitis, and gastroint...
Source: Journal of Autoimmunity - November 6, 2009 Category: Allergy & Immunology Authors: Agmon-Levin N, Shapira Y, Selmi C, Barzilai O, Ram M, Szyper-Kravitz M, Sella S, Katz BS, Youinou P, Renaudineau Y, Larida B, Invernizzi P, Gershwin ME, Shoenfeld Y Tags: J Autoimmun Source Type: journals

Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome. J Autoimmun. 2009 Nov 2; Authors: Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable degree of lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations. Minor salivary gland (MSG) lesions mainly consist of T and B cells, while antigen-presenting cells have been reported in heavy infiltrates. Evidence suggests that the infiltrate composition differs according to lesion sever...
Source: Journal of Autoimmunity - November 2, 2009 Category: Allergy & Immunology Authors: Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM Tags: J Autoimmun Source Type: journals

Adoptive transfer of IL-10-secreting CD4(+)CD49b(+) regulatory T cells suppresses ongoing arthritis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have previously demonstrated, in the collagen-induced arthritis model (CIA), that repetitive injections of immature bone-marrow-derived dendritic cells (iDCs) induce the expansion of a population of CD4CD49b-expressing cells, and that their adoptive transfer results in protection against CIA in a prophylactic setting. However, the in vivo mechanism responsible for their expansion, as well as their therapeutic potential in established disease remains to be defined. In the present study, we show that expression of the MHC class II molecules on iDCs is required for their expansion thus identifying these cells as MHC cl...
Source: Journal of Autoimmunity - October 30, 2009 Category: Allergy & Immunology Authors: Charbonnier LM, Han WG, Quentin J, Huizinga TW, Zwerina J, Toes RE, Jorgensen C, Louis-Plence P Tags: J Autoimmun Source Type: journals

The role of dendritic cell subsets in 2,4,6-trinitrobenzene sulfonic acid-induced ileitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dendritic cells (DCs) are widely distributed throughout the lymphoid and nonlymphoid tissues, and are important initiators of acquired immunity and also serve as regulators by inducing self-tolerance. However, it has not been thoroughly clarified whether DCs are involved in the termination of immune responses. In this paper, we have examined the kinetical movement of dendritic cells (DCs) in the lamina propria using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ileitis model (an animal model for Crohn's disease). Increased numbers of DCs were recruited to the inflammatory sites from day 1 to day 3 at which tim...
Source: Journal of Autoimmunity - October 29, 2009 Category: Allergy & Immunology Authors: Hoshino S, Inaba M, Iwai H, Ito T, Li M, Eric Gershwin M, Okazaki K, Ikehara S Tags: J Autoimmun Source Type: journals

The clinical spectrum and immunobiology of parainfectious neuromyelitis optica (Devic) syndromes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In a subgroup of patients with neuromyelitis optica (NMO), a severe inflammatory demyelinating disorder of autoimmune origin characterized by recurrent attacks of optic neuritis and longitudinally extensive transverse myelitis, a parainfectious pathogenesis may play a central role. We systematically evaluated such reports in the literature published between 1975 and 2009 in order to characterize parainfectious NMO syndromes. Identified were 25 cases, whereof 11 were in association with viral and 14 with bacterial pathogens. Sufficient clinical and paraclinical information was available in 16 patients (11 women). Median...
Source: Journal of Autoimmunity - October 21, 2009 Category: Allergy & Immunology Authors: Sellner J, Hemmer B, Mühlau M Tags: J Autoimmun Source Type: journals

Autoimmunity in retinal degeneration: Autoimmune retinopathy and age-related macular degeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe how autoimmunity relates to the pathogenesis of AIR and AMD. We explain how the antigen microarray technique is used to detect autoantibodies in patient serum samples, and discuss how current animal models for AMD can be used to investigate autoimmune pathogenesis. Finally, we outline unanswered questions and exciting areas of future study related to autoimmune retinal degeneration. PMID: 19846275 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 18, 2009 Category: Allergy & Immunology Authors: Morohoshi K, Goodwin AM, Ohbayashi M, Ono SJ Tags: J Autoimmun Source Type: journals

Emerging roles of TLR7 and TLR9 in murine SLE.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by B cell hyperactivity leading to the production of various autoantibodies and subsequent development of glomerulonephritis, i.e. lupus nephritis. Among the principal targets of autoantibodies produced in murine SLE are nucleic acid-protein complexes, such as chromatin and ribonucleoproteins, and the envelope glycoprotein gp70 of endogenous retroviruses. The preferential production of these autoantibodies is apparently promoted by the presence of genetic abnormalities leading to defects in the elimination of apoptotic cells and to an enhanced e...
Source: Journal of Autoimmunity - October 18, 2009 Category: Allergy & Immunology Authors: Santiago-Raber ML, Baudino L, Izui S Tags: J Autoimmun Source Type: journals

Serum inflammatory cytokines, complement components, and soluble interleukin 2 receptor in primary biliary cirrhosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, PBC sera manifest higher levels of sIL-2R and complement components and this may reflect a perpetuated immune activation. As expected, we also report that all major pro-inflammatory cytokine levels are enhanced in PBC. Further longitudinal analyses could demonstrate a correlation between these markers and disease stage or inflammatory activity, to predict histological staging, disease activity, and response to treatment. PMID: 19846277 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 18, 2009 Category: Allergy & Immunology Authors: Barak V, Selmi C, Schlesinger M, Blank M, Agmon-Levin N, Kalickman I, Gershwin ME, Shoenfeld Y Tags: J Autoimmun Source Type: journals

Clustering and commonalities among autoimmune diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The concept that autoimmune diseases are characterized by shared (common) threads is well illustrated by their propensity to co-associate in a patient or direct relatives, as coexistences or overlaps. Recognized are two major autoimmune clusters, "thyrogastric" (mostly organ-specific) and "lupus-associated" (mostly multisystem). Additionally, some autoimmune diseases distribute within either cluster and a few appear not to associate. Also, within each cluster there are overlaps constituting virtually a distinct syndrome. These patterns of coexistence/overlaps depend predominantly on genetic determinants as judged by da...
Source: Journal of Autoimmunity - October 15, 2009 Category: Allergy & Immunology Authors: Mackay IR Tags: J Autoimmun Source Type: journals

Autoimmune thyroiditis: A model uniquely suited to probe regulatory T cell function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Murine experimental autoimmune thyroiditis (EAT) is a model for Hashimoto's thyroiditis that has served as a prototype of T cell-mediated autoimmunity for more than three decades. Key roles for MHC restriction and autoantigen influence on susceptibility to autoimmunity have been demonstrated in EAT. Moreover, it has served a unique role in investigations of self tolerance. In the early 1980s, self tolerance and resistance to EAT induction could be enhanced by increasing circulating levels of the autoantigen, thyroglobulin (Tg), by exogenous addition as well as endogenous release. This observation, directly linking circ...
Source: Journal of Autoimmunity - October 9, 2009 Category: Allergy & Immunology Authors: Kong YC, Morris GP, Brown NK, Yan Y, Flynn JC, David CS Tags: J Autoimmun Source Type: journals

Alternatively activated macrophages in infection and autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Macrophages are innate immune cells that play an important role in activation of the immune response and wound healing. Pathogens that require T helper-type 2 (Th2) responses for effective clearance, such as parasitic worms, are strong inducers of alternatively activated or M2 macrophages. However, infections such as bacteria and viruses that require Th1-type responses may induce M2 as a strategy to evade the immune system. M2 are particularly efficient at scavenging self tissues following injury through receptors like the mannose receptor and scavenger receptor-A. Thus, M2 may increase autoimmune disease by presenting...
Source: Journal of Autoimmunity - October 8, 2009 Category: Allergy & Immunology Authors: Fairweather D, Cihakova D Tags: J Autoimmun Source Type: journals

Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Previous studies have estimated a prevalence of a broad grouping of autoimmune diseases of 3.2%, based on literature review of studies published between 1965 and 1995, and 5.3%, based on national hospitalization registry data in Denmark. We examine more recent studies pertaining to the prevalence of 29 autoimmune diseases, and use these data to correct for the underascertainment of some diseases in the hospitalization registry data. This analysis results in an estimated prevalence of 7.6-9.4%, depending on the size of the correction factor used. The rates for most diseases for which data are available from many geograp...
Source: Journal of Autoimmunity - October 7, 2009 Category: Allergy & Immunology Authors: Cooper GS, Bynum ML, Somers EC Tags: J Autoimmun Source Type: journals

Autoimmune response induced by dendritic cells exerts anti-tumor effect in murine model of leukemia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, high titers of anti-ds DNA antibodies were induced after injecting syngeneic dendritic cells into BALB/c mice. In addition, mice immunized with DCs showed the inhibition of RL male symbol 1, BALB/c leukemia cell line, tumor growth, and prolonged survival times of tumor mice but no significant difference was found in specific CTL response and NK cell activity when compared to those of the control group. Anti-ds DNA monoclonal antibodies can recognize RL male symbol 1 cells but not normal cells by FACS analysis. Monoclonal anti-ds DNA antibody was demonstrated to be able to lyse tumor cells via complement medi...
Source: Journal of Autoimmunity - October 6, 2009 Category: Allergy & Immunology Authors: Tsai BY, Lin YL, Chiang BL Tags: J Autoimmun Source Type: journals

Environmental triggers of autoimmune thyroiditis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger for autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in gene...
Source: Journal of Autoimmunity - October 6, 2009 Category: Allergy & Immunology Authors: Burek CL, Talor MV Tags: J Autoimmun Source Type: journals

Spontaneous autoimmune myocarditis and cardiomyopathy in HLA-DQ8.NODAbo transgenic mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most individuals have viral infections at some point in their life, however, only few develop autoreactivity to cardiac myosin following infection suggesting a genetic predisposition. Population studies have shown that among all the genetic factors linked with autoimmune disease development, MHC class II genes are the most significant genetic factors. Experimental autoimmune myocarditis resembling human Dilated cardiomyopathy can be induced in susceptible mice by infection with coxsackie virus as well as immunization with purified foreign and murine cardiac specific a-myosin. We generated transgenic mice lacking endoge...
Source: Journal of Autoimmunity - October 4, 2009 Category: Allergy & Immunology Authors: Taneja V, David CS Tags: J Autoimmun Source Type: journals

Self heat-shock protein 65-mediated regulation of autoimmune arthritis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Heat-shock proteins (Hsps) have been invoked in the pathogenesis of a variety of autoimmune diseases. The mycobacterial heat-shock protein 65 (Bhsp65) has been studied extensively as one of the antigenic triggers of autoimmunity in experimental models of, as well as patients with, rheumatoid arthritis. As Hsps are highly conserved and immunogenic, it is generally anticipated that self Hsps might serve as the endogenous targets of the immune response initiated by the homologous foreign Hsps. Contrary to this expectation, studies in the rat adjuvant arthritis (AA) model have revealed that priming of the self (rat) hsp65 ...
Source: Journal of Autoimmunity - September 30, 2009 Category: Allergy & Immunology Authors: Durai M, Huang MN, Moudgil KD Tags: J Autoimmun Source Type: journals

Sjögren syndrome: Advances in the pathogenesis from animal models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sjögren syndrome: Advances in the pathogenesis from animal models. J Autoimmun. 2009 Oct 1; Authors: Chiorini JA, Cihakova D, Ouellette CE, Caturegli P Sjögren syndrome is an autoimmune disease characterized by hyposecretion of the lacrimal and salivary glands, resulting in dryness of the eyes and mouth. Individuals may experience primary Sjögren syndrome or a secondary form accompanying another rheumatic autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus. The pathogenic mechanisms of Sjögren syndrome remain largely unknown, in part a consequence of the heteroge...
Source: Journal of Autoimmunity - September 30, 2009 Category: Allergy & Immunology Authors: Chiorini JA, Cihakova D, Ouellette CE, Caturegli P Tags: J Autoimmun Source Type: journals

Consideration of strategies for hematopoietic cell transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bone marrow transplantation has been adoptively transferred from oncology to the treatment of autoimmune disorders. Along with extension of prevalent transplant-related concepts, the assumed mechanism that arrests autoimmunity involves elimination of pathogenic cells and resetting of immune homeostasis. Similar to graft versus tumor (GVT) reactivity, allogeneic transplants are considered to provide a better platform of immunomodulation to induce a graft versus autoimmunity reaction (GVA). It is yet unclear whether recurrence of autoimmunity in both autologous and allogeneic settings reflects relapse of the disease, tra...
Source: Journal of Autoimmunity - September 30, 2009 Category: Allergy & Immunology Authors: Yaniv I, Ash S, Farkas DL, Askenasy N, Stein J Tags: J Autoimmun Source Type: journals

Matrix metalloproteinase and G protein coupled receptors: Co-conspirators in the pathogenesis of autoimmune disease and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Similarities in the pathologies of autoimmune diseases and cancer have been noted for at least 30 years. Inflammatory cytokines and growth factors mediate cell proliferation, and proteinases, especially the collagenase, Matrix Metalloproteinase-1 (MMP-1), contribute to disease progression by remodeling the extracellular matrix and modulating the microenvironment. This review focuses on two cancers (melanoma and breast) and on the autoimmune disorder, rheumatoid arthritis (RA), and discusses the activated stromal cells found in these diseases. MMP-1 was originally thought to function only to degrade interstitial collage...
Source: Journal of Autoimmunity - September 29, 2009 Category: Allergy & Immunology Authors: Eck SM, Blackburn JS, Schmucker AC, Burrage PS, Brinckerhoff CE Tags: J Autoimmun Source Type: journals

A recombinant heavy chain antibody approach blocks ART2 mediated deletion of an iNKT cell population that upon activation inhibits autoimmune diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ectoenzyme ADP-ribosyltransferase 2.2 (ART2.2) can apoptotically delete various T-cell subsets. Depending on the involved apoptotic T-cell subset, enhanced ART2.2 activity could result in immunosuppression or autoimmunity. Diminished activity of the CD38 ectoenzyme that normally represents a counter-regulatory competitor for the NAD substrate represents one mechanism enhancing ART2.2 activity. Hence, it would be desirable to develop an agent that efficiently blocks ART2.2 activity in vivo. While the llama derived recombinant s+16 single domain antibody overcame the difficulty of specifically targeting the ART2.2 ca...
Source: Journal of Autoimmunity - September 28, 2009 Category: Allergy & Immunology Authors: Scheuplein F, Rissiek B, Driver JP, Chen YG, Koch-Nolte F, Serreze DV Tags: J Autoimmun Source Type: journals

Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: We identify and replicate the association of the C8orf13-BLK region as a novel susceptibility factor for SSc, placing it in the category of common autoimmune disease susceptibility genes. PMID: 19796918 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 28, 2009 Category: Allergy & Immunology Authors: Gourh P, Agarwal SK, Martin E, Divecha D, Rueda B, Bunting H, Assassi S, Paz G, Shete S, McNearney T, Draeger H, Reveille JD, Radstake TR, Simeon CP, Rodriguez L, Vicente E, Gonzalez-Gay MA, Mayes MD, Tan FK, Martin J, Arnett FC Tags: J Autoimmun Source Type: journals

Aetiopathogenesis of autoimmune hepatitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interface hepatitis, histological hallmark of autoimmune hepatitis (AIH), is a dense portal mononuclear cell infiltrate invading the parenchyma, consisting of CD4 and CD8 T-lymphocytes, monocytes/macrophages and plasma cells. What triggers AIH is unknown, but there is evidence that failure of immune homeostasis plays a permissive role allowing liver autoantigen-specific cells to attack hepatocytes. Damage is likely to be orchestrated by CD4 T-lymphocytes recognizing an autoantigenic liver peptide. For autoimmunity to arise, the peptide, embraced by an HLA class II molecule, must be presented to naïve CD4 T-helper ...
Source: Journal of Autoimmunity - September 16, 2009 Category: Allergy & Immunology Authors: Longhi MS, Ma Y, Mieli-Vergani G, Vergani D Tags: J Autoimmun Source Type: journals

Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The autoimmune-type Fcgr2b with deletion polymorphism in AP-4-binding site in the promoter region is suggested to be one most plausible susceptibility gene for systemic lupus erythematosus (SLE). We previously found that there is a strong epistatic interaction between the autoimmune-type Fcgr2b polymorphism and Y chromosome-linked autoimmune acceleration (Yaa) mutation, thus severe SLE observed in BXSB males neither develops in BXSB females nor in the congenic BXSB.IIB(B6) males carrying wild C57BL/6-type Fcgr2b. Present studies examined whether the wild-type Fcgr2b could suppress SLE in mice carrying Yaa-unrelated SLE...
Source: Journal of Autoimmunity - September 13, 2009 Category: Allergy & Immunology Authors: Lin Q, Hou R, Sato A, Ohtsuji M, Ohtsuji N, Nishikawa K, Tsurui H, Amano H, Amano E, Sudo K, Nishimura H, Shirai T, Hirose S Tags: J Autoimmun Source Type: journals

The role of chemokines in the recruitment of lymphocytes to the liver.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chemokines direct leukocyte trafficking and positioning within tissues. They thus play critical roles in regulating immune responses and inflammation. The chemokine system is complex involving interactions between multiple chemokines and their receptors that operate in combinatorial cascades with adhesion molecules. The involvement of multiple chemokines and chemokine receptors in these processes brings flexibility and specificity to recruitment. The hepatic vascular bed is a unique low flow environment through which leukocyte are recruited to the liver during homeostatic immune surveillance and in response to infectio...
Source: Journal of Autoimmunity - September 7, 2009 Category: Allergy & Immunology Authors: Oo YH, Adams DH Tags: J Autoimmun Source Type: journals

Association of T-cell reactivity with beta-cell function in recent onset type 1 diabetes patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: The number of detectable islet-reactive immune cells decreases within 1-2 years after diagnosis of type 1 diabetes. Cytokine production by antigen-specific PBMC reactivity is related to beta-cell function as measured by stimulated C-peptide. Cellular immunity appears to regress soon after disease diagnosis and begin of insulin therapy. PMID: 19744828 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 7, 2009 Category: Allergy & Immunology Authors: Pfleger C, Meierhoff G, Kolb H, Schloot NC, Tags: J Autoimmun Source Type: journals

CD8+ T cell tolerance following antigen recognition on hepatocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hepatocytes, the predominant cell type in the liver, are the main cell infected by the hepatitis C virus (HCV) and represent important targets for immune therapy. Although early studies suggested that this parenchymal cell expresses low levels of class I MHC molecules, hepatocytes are emerging as important players in intrahepatic immune responses. Not only do they express high levels of molecules important in antigen presentation, but their expression of these molecules in vivo is also polarized towards the lumen of the sinusoids, thus maximising the efficiency of T cell activation. Electron micrographs indicate that i...
Source: Journal of Autoimmunity - September 7, 2009 Category: Allergy & Immunology Authors: Holz LE, Warren A, Le Couteur DG, Bowen DG, Bertolino P Tags: J Autoimmun Source Type: journals

Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: Effects on uptake of oxidized LDL in macrophages as a potential mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages. PMID: 19726160 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - August 30, 2009 Category: Allergy & Immunology Authors: de Faire U, Su J, Hua X, Frostegård A, Halldin M, Hellenius ML, Wikström M, Dahlbom I, Grönlund H, Frostegård J Tags: J Autoimmun Source Type: journals

Development of a Murine model to dissect the CpG-oligonucleotide-enhancement of the killing of human B Cells by rituximab.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As a model to dissect the effects of CpG-oligonucleotides (CpG) on rituximab (RTX)-mediated therapeutic killing of autoimmune or malignant B lymphocytes, nude mice were grafted with Daudi human B cells. These mice were then injected with RTX alone or together with CpG. The human B cell aggregate was measured, and the reactive infiltrate analyzed after selective depletion of murine circulating cells. Macrophages (MØ) were identified in infiltrates, but not polymorphonuclear neutrophils (PMN), as confirmed by the failure of quantitative polymerase chain reaction to detect transcripts for PMN-specific myeloperoxidase...
Source: Journal of Autoimmunity - August 30, 2009 Category: Allergy & Immunology Authors: Buhé V, Pers JO, Marianowski R, Berthou C, Youinou P, Loisel S Tags: J Autoimmun Source Type: journals

CD4 T cells in hepatic immune tolerance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The liver features a unique immune microenvironment, which seems to favour immune tolerance, both locally and systemically. The hepatic microenvironment is formed by the unique anatomical structure of the liver sinusoids, a peculiar composition of antigen presenting cells and the relative abundance of anti-inflammatory cytokines. The outcome of T cell stimulation within the hepatic microenvironment is often tolerance. This is illustrated by the observations that antigen delivered to the portal vein, or allografts co-transplanted with allogeneic liver are not attacked by the immune system. Moreover, the tolerogenic prop...
Source: Journal of Autoimmunity - August 28, 2009 Category: Allergy & Immunology Authors: Carambia A, Herkel J Tags: J Autoimmun Source Type: journals

Immune tolerance: What is unique about the liver.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The 'liver tolerance effect' mediates local and systemic tolerance to self and foreign antigens and has been attributed to specialized resident cells expressing anti-inflammatory mediators and inhibitory cell surface ligands for T cell activation. Non-parenchymal liver cells responsible for the tolerogenic properties of the liver are the resident dendritic cells (DCs), which comprise myeloid as well as plasmacytoid DCs, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs) as well as hepatic stellate cells (HSCs), also known as Ito cells. These cells mediate immunosuppression by production of anti-inflammator...
Source: Journal of Autoimmunity - August 27, 2009 Category: Allergy & Immunology Authors: Tiegs G, Lohse AW Tags: J Autoimmun Source Type: journals

Impact of interleukin-6 classic- and trans-signaling on liver damage and regeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interleukin-6 (IL-6) has been suggested to play a pivotal role in liver regeneration. IL-6 on target cells activates a receptor complex consisting of the IL-6 receptor (IL-6R) and the signal transducing receptor subunit gp130. Not all cells in the body express the IL-6R on the cell surface. IL-6 can signal via two different pathways: classical signaling via the membrane bound IL-6R and IL-6 trans-signaling via a naturally occurring soluble IL-6R (sIL-6R). This second pathway widens the scope of IL-6 signaling since also cells expressing no membrane bound IL-6R can be stimulated by the trans-signal pathway. Mimicking IL...
Source: Journal of Autoimmunity - August 27, 2009 Category: Allergy & Immunology Authors: Drucker C, Gewiese J, Malchow S, Scheller J, Rose-John S Tags: J Autoimmun Source Type: journals

Viral triggers for autoimmunity: Is the 'glass of molecular mimicry' half full or half empty?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this review we want to consider some of the requirements for autoimmune disease to develop and how this may be reproduced in animal models. Besides a genetic predisposition, environmental triggering factors seem to play a central role in the etiology of many autoimmune diseases. In theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components. However, in order for such a process of molecular mimicry to induce autoimmunity the mechanisms of maintaining tolerance or ignorance to the self-com...
Source: Journal of Autoimmunity - August 25, 2009 Category: Allergy & Immunology Authors: Christen U, Hintermann E, Holdener M, von Herrath MG Tags: J Autoimmun Source Type: journals

High circulating levels of free interleukin-18 in patients with active SLE in the presence of elevated levels of interleukin-18 binding protein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies particularly to nuclear antigens and by an abnormal production of proinflammatory cytokines. In the present study, we measured the levels of the proinflammatory cytokine IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP), in sera of SLE patients at various stages of the disease. This is the first study to present IL-18BP levels in sera of SLE patients as well as the calculated, biologically active, free IL-18 concentrations that are most probably more relevant to the pathology of SLE. Sera fro...
Source: Journal of Autoimmunity - August 19, 2009 Category: Allergy & Immunology Authors: Novick D, Elbirt D, Miller G, Dinarello CA, Rubinstein M, Sthoeger ZM Tags: J Autoimmun Source Type: journals

SLA/LP/tRNP((Ser)Sec) antigen in autoimmune hepatitis: Identification of the native protein in human hepatic cell extract.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A diagnostic subgroup of AIH type 1 is characterized by specific serum antibodies against soluble liver protein. The respective autoantigen was named SLA/LP/tRNP((Ser)Sec), after three homologous recombinant polypeptides were isolated from expression gene libraries. We analyzed human cultured liver cells for the human homologue of recombinant SLA/LP/tRNP((Ser)Sec) by antigen purification. In addition, a monoclonal antibody was generated against recombinant SLA-p35, a truncated recombinant SLA-reactive polypeptide. With a positive patient serum, immune affinity chromatography was performed on the 52 kD-SLA main antigeni...
Source: Journal of Autoimmunity - August 12, 2009 Category: Allergy & Immunology Authors: Volkmann M, Luithle D, Zentgraf H, Schnölzer M, Fiedler S, Heid H, Schulze-Bergkamen A, Strassburg CP, Gehrke SG, Manns MP Tags: J Autoimmun Source Type: journals

Navigating the passage between Charybdis and Scylla: Recognizing the achievements of Noel Rose.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This special edition of the Journal of Autoimmunity is dedicated to celebrate the enormous contributions of Dr. Noel Rose, a physician-scientist, someone that can be readily anointed as a gifted scientist who laid down the foundation and fundamental concepts of human autoimmunity. Dr. Rose performed a series of landmark studies that extend back more than 50 years and whose work is the cornerstone of the commonly used term "from the bench to the bedside." The studies included not only characterization of a normal immune response but, more importantly, defining the nature of not only the antigen, but also the aberrant re...
Source: Journal of Autoimmunity - August 11, 2009 Category: Allergy & Immunology Authors: Ansari AA, Gershwin ME Tags: J Autoimmun Source Type: journals

The genetics of human autoimmune disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autoimmune diseases are known to have a multifactorial pathogenesis, with both environmental and inherited components. Wide technical progresses together with the completion of the sequencing of human genome have recently allowed the identification of new genetic risk variants in many autoimmune disorders. While part of these studies confirmed previous knowledge, most of the data has disclosed novel and unsuspected roles in the development of autoimmunity for molecules involved in various pathogenic pathways. After the current first wave of data from high-density genome-wide studies, we now need to further characterize...
Source: Journal of Autoimmunity - August 11, 2009 Category: Allergy & Immunology Authors: Invernizzi P, Gershwin ME Tags: J Autoimmun Source Type: journals

Application of tissue-specific NK and NKT cell activity for tumor immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Natural killer (NK) and NKT cells are a first line of defense against pathogens and transformed cells. However, dysregulation of their function can lead to autoimmune disease. A better understanding of the mechanisms controlling NK and NKT effector function should lead to the development of improved strategies for the treatment of many diseases. The site in which NK and NKT cells reside should be taken into account, because accumulating evidence suggests that the tissue microenvironment strongly influences their function. In this regard, the liver represents a unique immunologic organ in which the balance between the n...
Source: Journal of Autoimmunity - August 11, 2009 Category: Allergy & Immunology Authors: Subleski JJ, Wiltrout RH, Weiss JM Tags: J Autoimmun Source Type: journals

Autoimmune myocarditis: Past, present and future.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present current animal models and describe possible experimental approaches to improve diagnosis. Finally, we give an outlook on possible drug targets by describing the latest findings in the animal models focussing on chemokines and cytokines, T cell responses and interactions, tolerance induction and the development of autoantibodies. PMID: 19679447 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - August 10, 2009 Category: Allergy & Immunology Authors: Leuschner F, Katus HA, Kaya Z Tags: J Autoimmun Source Type: journals

CTLA4-Ig modifies dendritic cells from mice with collagen-induced arthritis to increase the CD4+CD25+Foxp3+ regulatory T cell population.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we investigated the influence of CTLA4-Ig on the CD4+CD25+Foxp3+ Treg population in collagen-induced arthritis (CIA) mouse model. CTLA4-Ig suppressed CIA and increased the CD4+CD25+Foxp3+ Treg population in joint and spleen. When CD11c + DCs and CD4+T cells from CIA mice were cultured with anti-CD3, CTLA4-Ig increased the CD4+CD25 + Foxp3+ Treg population in a TGF-beta-dependent manner. When CD11c + DCs from CIA mice were treated with CTLA4-Ig and adoptively transferred into CIA-induced mice, arthritis did not develop in association with the increase in CD4+CD25+Foxp3+ Treg population. However, in CTLA4-Ig-u...
Source: Journal of Autoimmunity - August 6, 2009 Category: Allergy & Immunology Authors: Ko HJ, Cho ML, Lee SY, Oh HJ, Heo YJ, Moon YM, Kang CM, Kwok SK, Ju JH, Park SH, Park KS, Kim HY Tags: J Autoimmun Source Type: journals

Roles for cathepsins S, L, and B in insulitis and diabetes in the NOD mouse.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We developed a panel of non-obese diabetic (NOD) mice deficient in major lysosomal cysteine proteases (cathepsins S, L and B) to identify protease enzymes essential for autoimmune diabetes. Null alleles for cathepsins (Cts) S, L or B were introgressed onto the NOD genetic background with 19 Idd markers at homozygosity. Diabetes onset was determined among females aged up to 6 months. We evaluated insulitis and sialadenitis in tissues using histology and computer assisted morphology. NOD mice deficient in Ctss or Ctsb were partially protected from diabetes with incidence at 33% and 28%, respectively, versus wild-type NOD...
Source: Journal of Autoimmunity - August 4, 2009 Category: Allergy & Immunology Authors: Hsing LC, Kirk EA, McMillen TS, Hsiao SH, Caldwell M, Houston B, Rudensky AY, Leboeuf RC Tags: J Autoimmun Source Type: journals

Patients with antiphospholipid syndrome display endothelial perturbation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: As a whole these findings indicate that APS patients display an endothelial perturbation in the absence of other detectable traditional risk factors for atherosclerosis. PMID: 19656656 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - August 2, 2009 Category: Allergy & Immunology Authors: Cugno M, Borghi MO, Lonati LM, Ghiadoni L, Gerosa M, Grossi C, De Angelis V, Magnaghi G, Tincani A, Mari D, Riboldi P, Meroni PL Tags: J Autoimmun Source Type: journals

AIRE deficiency leads to impaired iNKT cell development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autoimmune Polyendocrine Syndrome type I (APS I) is caused by mutations in the Autoimmune Regulator gene (AIRE), and results in the immunological destruction of endocrine organs. Herein we have characterized the CD1d-restricted invariant NKT cells (iNKT) and NK cells in APS I patients and Aire(-/-) mice, two cell populations known to play a role in the regulation of autoimmune disease. We show that the frequency of circulating iNKT cells is reduced in APS I patients compared to healthy controls. In accordance with this, iNKT cells are significantly reduced in the thymus and peripheral organs of Aire(-/-) mice. Bone mar...
Source: Journal of Autoimmunity - July 31, 2009 Category: Allergy & Immunology Authors: Lindh E, Rosmaraki E, Berg L, Brauner H, Karlsson MC, Peltonen L, Höglund P, Winqvist O Tags: J Autoimmun Source Type: journals

Primary Ovarian Insufficiency: X chromosome defects and autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women <40 years. The most severe forms present with absent pubertal development and primary amenorrhea, whereas forms with post-pubertal onset ...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Persani L, Rossetti R, Cacciatore C, Bonomi M Tags: J Autoimmun Source Type: journals

Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): immunomodulation of gene expression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by dysregulation of cytokines, apoptosis, and B- and T-cell functions. The tolerogenic peptide, hCDR1 (Edratide), ameliorated the clinical manifestations of murine lupus via down-regulation of pro-inflammatory cytokines and apoptosis, up-regulation of the immunosuppressive cytokine TGF-beta, and the induction of regulatory T-cells. In the present study, gene expression was determined in peripheral blood mononuclear cells of 9 lupus patients that were treated for 26 weeks with either hCDR1 (five patients), or placebo (four patients). Disease acti...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Sthoeger ZM, Sharabi A, Molad Y, Asher I, Zinger H, Dayan M, Mozes E Tags: J Autoimmun Source Type: journals

Autoimmune stigmata in Turner syndrome: when lacks an X chromosome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An increased frequency of autoimmune diseases as well as an elevated incidence of autoantibodies has been observed in patients with Turner syndrome; the most common autoimmune diseases appear to be thyroid autoimmune disease and inflammatory bowel diseases. Turner patients evolve towards autoimmunity much more frequently than people with normal karyotype without any relevant excess of the putative immunogenetic risk markers. That underscores the great influence of X-chromosome abnormalities in the development of autoimmune disorders and suggests an epistatic interaction of X genes with immune response genes. Interestin...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Larizza D, Calcaterra V, Martinetti M Tags: J Autoimmun Source Type: journals

The genetics and epigenetics of autoimmune diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article will review current understanding of the genetics and epigenetics of lupus, rheumatoid arthritis, multiple sclerosis and type 1 diabetes, using systemic lupus erythematosus as the primary example. Other autoimmune diseases may have a similar foundation. PMID: 19349147 [PubMed - in process] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Hewagama A, Richardson B Tags: J Autoimmun Source Type: journals

Female predominance and X chromosome defects in autoimmune diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is known that autoimmune diseases cumulatively affect 5-10% of the general population. Although knowledge of pathogenesis has become more refined, laboratory diagnosis more accurate, and therapy more effective, the reasons for the female preponderance of these conditions remain unclear. The most intriguing theory to explain the female preponderance is currently related to sex chromosomes, as women with autoimmune diseases manifest a higher rate of circulating cells with a single X chromosome (i.e. X monosomy). In addition, there have been several reports on the role of X chromosome gene dosage through inactivation o...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Invernizzi P, Pasini S, Selmi C, Gershwin ME, Podda M Tags: J Autoimmun Source Type: journals

X-linked primary immunodeficiencies as a bridge to better understanding X-chromosome related autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies indicate that genes located on the X-chromosome play a major and unique role in autoimmunity. The fact that most X-linked primary immune deficiencies carry significant autoimmune manifestations greatly supports this notion. Autoimmunity and immune deficiency have been considered two opposite extremes resulting from immune dysregulation and failure of immune development and/or function, respectively. Growing evidence has been accumulating to indicate that autoimmune phenomena occur in patients suffering from primary immune deficiency (PID), and the molecular and cellular mechanisms that interconnect these...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Pessach IM, Notarangelo LD Tags: J Autoimmun Source Type: journals

Naturally-existing CD4(+)CD25(+)Foxp3(+) regulatory T cells are required for tolerance to experimental autoimmune thyroiditis induced by either exogenous or endogenous autoantigen.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Murine experimental autoimmune thyroiditis (EAT) is a model for Hashimoto's thyroiditis, an organ-specific autoimmune disease characterized by mononuclear cell infiltration and destruction of the thyroid gland. Susceptibility to EAT is MHC-linked, and influenced by CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Treg depletion enables thyroiditis induction with mouse thyroglobulin (mTg) in traditionally-resistant mice and mTg-induced, Treg-mediated tolerance protects against EAT induction in genetically-susceptible mice. Here, we demonstrate the existence of naturally-existing CD4(+)CD25(+)Foxp3(+) Tregs (nTregs) inf...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Morris GP, Brown NK, Kong YC Tags: J Autoimmun Source Type: journals

Future directions in genetic for autoimmune diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autoimmune diseases affect cumulatively 5-10% of the general population and are multifactorial in their pathogenesis, with both inherited and environmental components. Although our knowledge of their pathogenesis has become more refined, diagnosis more accurate, and therapy more effective, the reasons for their development and the female preponderance of these diseases are still unknown. One of the most intriguing hypothesis to explain the female preponderance is related to sex chromosomes, as women affected by autoimmune diseases have a higher rate of circulating cells with a single X chromosome. In addition, a number...
Source: Journal of Autoimmunity - June 27, 2009 Category: Allergy & Immunology Authors: Invernizzi P Tags: J Autoimmun Source Type: journals