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Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices ...
Source: Clinical Immunology - November 13, 2009 Category: Allergy & Immunology Authors: Yong PL, Boyle J, Ballow M, Boyle M, Berger M, Bleesing J, Bonilla FA, Chinen J, Cunninghamm-Rundles C, Fuleihan R, Nelson L, Wasserman RL, Williams KC, Orange JS Tags: Clin Immunol Source Type: journals

Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Augmented intestinal T cells, especially CD4(+)T cells, are involved in the pathogenesis of inflammatory bowel disease (IBD). We used a murine 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model to investigate whether Tim-3, a negative regulator of CD4(+)T cells, is involved in the suppression of IBD. We found that blocking the Tim-3 signal pathway exacerbated TNBS-induced colitis, as shown by increased weight loss and aggravated tissue injury. Blockade of the Tim-3 pathway resulted in an increase in Tim-3(+)CD4T cells, a biased T effector cell response, and a decrease in Treg cells. It also resulted in ...
Source: Clinical Immunology - November 12, 2009 Category: Allergy & Immunology Authors: Li X, Chen G, Li Y, Wang R, Wang L, Lin Z, Gao X, Feng J, Ma Y, Shen B, Li Y, Han G Tags: Clin Immunol Source Type: journals

Advanced glycation end products enhance monocyte activation during human mixed lymphocyte reaction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Posttransplant diabetes mellitus (PTDM) is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor (RAGE) on monocytes/macrophages plays roles in the diabetes complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, leading to reduced allograft survival. We investigated the effect of four distinct AGE subtypes (AGE-2/AGE-3/AGE-4/AGE-5) on the expressions of intracellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 on monocytes, the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)...
Source: Clinical Immunology - November 12, 2009 Category: Allergy & Immunology Authors: Ohashi K, Takahashi HK, Mori S, Liu K, Wake H, Sadamori H, Matsuda H, Yagi T, Yoshino T, Nishibori M, Tanaka N Tags: Clin Immunol Source Type: journals

Laboratory diagnosis of specific antibody deficiency to pneumococcal capsular polysaccharide antigens by multiplexed bead assay.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We evaluated a multiplexed bead-based assay (xMAP(R) Pneumococcal Immunity assay from Luminex) for the simultaneous determination of antibodies against 14 capsular polysaccharides. Post-vaccination (Pneumovax(R)) antibody concentrations were measured in 35 healthy children, 40 healthy adults, 99 consecutive patients with increased susceptibility to respiratory infection, and 24 patients with a deficient anti-polysaccharide antibody response. The serotype-specific lower 5th percentile (cutoff) value for the post-immunization antibody concentration was determined in healthy individuals. Eleven of 99 patients (11%) failed...
Source: Clinical Immunology - November 12, 2009 Category: Allergy & Immunology Authors: Borgers H, Moens L, Picard C, Jeurissen A, Raes M, Sauer K, Proesmans M, De Boeck K, Casanova JL, Meyts I, Bossuyt X Tags: Clin Immunol Source Type: journals

HCV-related hepatocellular carcinoma: From chronic inflammation to cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hepatitis C virus (HCV) infection is a worldwide health problem because of its incidence and pathogenicity. It might evolve into chronic disease, cirrhosis, and/or hepatocellular carcinoma (HCC) and the outcome is mainly determined by the host immune response. For viral clearance, combined innate and adaptive immune responses are required; resolution requires a vigorous, durable, polyclonal CD4(+) and CD8(+) T-cell response, with an increase in virus-specific CD8(+) T cells or cytotoxic T lymphocytes. Failure of efficient immune response can lead to chronic inflammation, tissue remodeling through cell growth, apoptosis...
Source: Clinical Immunology - November 10, 2009 Category: Allergy & Immunology Authors: Castello G, Scala S, Palmieri G, Curley SA, Izzo F Tags: Clin Immunol Source Type: journals

IFNbeta-1a therapy for multiple sclerosis expands regulatory CD8(+) T cells and decreases memory CD8(+) subset: A longitudinal 1-year study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The beneficial effects of interferon beta-1a (IFNbeta-1a) in multiple sclerosis (MS) remain only partially understood. CD8(+) T cells are key cells in MS pathogenesis that contribute to axonal damage in MS, whereas CD4(+) regulatory T cells (T(Reg)) and CD8(+) regulatory/suppressor T cells (Ts) play an important role in protecting against subsequent MS activity. We analysed ex vivo changes on T(Reg) and on the different subsets of CD4(+) and CD8(+) T lymphocytes, before IFNbeta-1a (Rebif) therapy and at 3, 6, and 12 months after treatment, in 23 MS patients and in 26 healthy controls. IFNbeta-1a significantly increased...
Source: Clinical Immunology - November 8, 2009 Category: Allergy & Immunology Authors: Aristimuño C, de Andrés C, Bartolomé M, de Las Heras V, Martínez-Ginés ML, Arroyo R, Fernández-Cruz E, Sánchez-Ramón S Tags: Clin Immunol Source Type: journals

Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infectious complications of the lung occur quite frequently in patients with common variable immunodeficiency (CVID), a clinical syndrome that represents a primary immunodeficiency. However, there appears to be noninfectious pulmonary complications in association with CVID as well, and recently the term granulomatous-lymphocytic interstitial lung disease (GLILD) has been created to describe these noninfectious, diffuse lung disease complications that develop in CVID patients. They exhibit both granulomatous and lymphoproliferative histologic patterns, consisting of lymphocytic interstitial pneumonia (LIP), follicular b...
Source: Clinical Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Park JH, Levinson AI Tags: Clin Immunol Source Type: journals

Elevated expression of Foxp3 in tumor-infiltrating Treg cells suppresses T-cell proliferation and contributes to gastric cancer progression in a COX-2-dependent manner.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transcription factor Foxp3 plays a key role in CD4(+)CD25(+) regulatory T (Treg) cell function. A correlation has been shown between survival and the frequency of tumor-infiltrating Foxp3-positive Treg cells in cancer patients. However, few studies have characterized the regulation of Foxp3 expression and function in Treg cells, which are known to comprise distinct subsets, with different roles in the complex tumor microenvironment. Here, we show that significantly more Foxp3-positive Treg cells accumulated in gastric tumors. In addition, we found increased expression of Foxp3 protein per cell in tumor-infiltrating...
Source: Clinical Immunology - November 7, 2009 Category: Allergy & Immunology Authors: Yuan XL, Chen L, Li MX, Dong P, Xue J, Wang J, Zhang TT, Wang XA, Zhang FM, Ge HL, Shen LS, Xu D Tags: Clin Immunol Source Type: journals

Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immunogenicity, manufacturing feasibility, and safety of a novel, autologous dendritic cell (DC)-based immunotherapy (AGS-004) was evaluated in ten human immunodeficiency virus type 1 (HIV-1)-infected adults successfully treated with antiretroviral therapy (ART). Personalized AGS-004 was produced from autologous monocyte-derived DCs electroporated with RNA encoding CD40L and HIV antigens (Gag, Vpr, Rev, and Nef) derived from each subjects' pre-ART plasma. Patients received monthly injections of AGS-004 in combination with ART. AGS-004 was produced within a mean of 6 weeks and yielded 4-12 doses/subject Full or partial ...
Source: Clinical Immunology - November 2, 2009 Category: Allergy & Immunology Authors: Routy JP, Boulassel MR, Yassine-Diab B, Nicolette C, Healey D, Jain R, Landry C, Yegorov O, Tcherepanova I, Monesmith T, Finke L, Sékaly RP Tags: Clin Immunol Source Type: journals

NK cell activation by KIR-binding antibody 1-7F9 and response to HIV-infected autologous cells in viremic and controller HIV-infected patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Natural killer (NK) cells may be protective in HIV infection and are inhibited by killer cell immunoglobulin-like receptors (KIRs) interacting with MHC class I molecules, including HLA-C. Retention of HLA-C despite downregulation of other MHC class I molecules on HIV infected cells might protect infected cells from NK cell recognition in vitro. To assess the role of inhibitory HLA-C ligands in the capacity of NK cells to recognize autologous infected T cells, we measured NK cell degranulation in vitro in viremic patients, controllers with low viremia, and healthy donors. No difference in NK cell response to uninfected ...
Source: Clinical Immunology - October 30, 2009 Category: Allergy & Immunology Authors: Johansson SE, Hejdeman B, Hinkula J, Johansson MH, Romagné F, Wahren B, Wagtmann NR, Kärre K, Berg L Tags: Clin Immunol Source Type: journals

Distribution of circulating cells in systemic juvenile idiopathic arthritis across disease activity states.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Juvenile idiopathic arthritis (JIA) encompasses a group of chronic childhood arthritides of unknown etiology. One subtype, systemic JIA (SJIA), is characterized by a combination of arthritis and systemic inflammation. Its systemic nature suggests that clues to SJIA pathogenesis may be found in examination of peripheral blood cells. To determine the immunophenotypic profiles of circulating mononuclear cells in SJIA patients with different degrees of disease activity, we studied PBMC from 31 SJIA patients, 20 polyarticular JIA patients (similar to adult rheumatoid arthritis), and 31 age-matched controls. During SJIA dise...
Source: Clinical Immunology - October 28, 2009 Category: Allergy & Immunology Authors: Macaubas C, Nguyen K, Deshpande C, Phillips C, Peck A, Lee T, Park JL, Sandborg C, Mellins ED Tags: Clin Immunol Source Type: journals

IL-15 promotes regulatory T cell function and protects against diabetes development in NK-depleted NOD mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IL-15, an anti-apoptotic cytokine, has been reported to promote the survival and function of NK cells and T cells, including regulatory T cells (Tregs). Here we examined the effect of repeated injections of IL-15 on the development of diabetes in NOD mice. Injection of recombinant murine IL-15, once a day for 2 weeks, neither inhibited nor accelerated diabetes development in untreated NOD mice. However, treatment with IL-15 significantly reduced the incidence and delayed the onset of diabetes in NOD mice that were depleted of NK cells, while NK cell depletion alone had no protection against the disease development. The...
Source: Clinical Immunology - October 27, 2009 Category: Allergy & Immunology Authors: Xia J, Liu W, Hu B, Tian Z, Yang Y Tags: Clin Immunol Source Type: journals

Essential and synergistic roles of IL1 and IL6 in human Th17 differentiation directed by TLR ligand-activated dendritic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Requirements for human Th17 differentiation in the context of activated dendritic cells (DCs) are still emerging. Here, we demonstrate that several Toll-like receptor (TLR) ligands, particularly LPS and a synthetic lipoprotein, activate human DCs to direct increased human Th17 differentiation. Based on neutralization studies, IL1, IL6, and TGFbeta contributed to human Th17 differentiation induced by LPS-activated DCs. Furthermore, TLR ligand-activated DCs produced high levels of IL6 and low levels of IL1beta. In an antigen presenting cell (APC)-free system, the minimum requirements identified for human Th17 differentia...
Source: Clinical Immunology - October 22, 2009 Category: Allergy & Immunology Authors: Benwell RK, Lee DR Tags: Clin Immunol Source Type: journals

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: Safety and immunogenicity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination. PMID: 19846344 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - October 19, 2009 Category: Allergy & Immunology Authors: Salemi S, Picchianti-Diamanti A, Germano V, Donatelli I, Di Martino A, Facchini M, Nisini R, Biselli R, Ferlito C, Podestà E, Cappella A, Milanetti F, Rossi F, Amodeo R, Tabacco F, Di Rosa R, Laganà B, D Amelio R Tags: Clin Immunol Source Type: journals

Serum BAFF and APRIL levels in patients with PBC.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
B-cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are known to be involved in the occurrence of autoimmune diseases. We assessed serum levels of these cytokines in PBC patients. Serum BAFF levels were significantly higher in PBC patients than in healthy controls (1253.9+/-741.4 vs. 722.8+/-199.2 pg/ml; p<0.0001) and HCV-infected patients (1253.9+/-741.4 vs. 871.0+/-251.1 pg/ml; p=0.015). Whereas changes in serum APRIL levels were not significant among these groups, there was a significant correlation between BAFF and AST (R=0.278, p=0.003) or total bilirubin (R=0...
Source: Clinical Immunology - October 16, 2009 Category: Allergy & Immunology Authors: Migita K, Ilyassova B, Kovzel EF, Nersesov A, Abiru S, Maeda Y, Komori A, Ito M, Yano K, Yatsuhashi H, Shimoda S, Ishibashi H, Nakamura M Tags: Clin Immunol Source Type: journals

Small for gestational age (SGA) neonates show reduced suppressive activity of their regulatory T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined whether complications such as reduced birth weight or the occurrence of preterm labor were associated with deficiencies in the number or in the immunosuppressive activity of Tregs in the fetal circulation. Their total number did not change during normal or complicated pregnancy. In contrast, their level of FoxP3 expression decreased continuously with gestational age and was significantly reduced in the presence of spontaneous term, but not preterm labor. In small for gestational age (SGA) neonates, FoxP3 expression was constantly decreased when compared to age matched healthy neonates. In accordance with the lo...
Source: Clinical Immunology - October 14, 2009 Category: Allergy & Immunology Authors: Steinborn A, Engst M, Haensch GM, Mahnke K, Schmitt E, Meuer S, Sohn C Tags: Clin Immunol Source Type: journals

Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The way in which anti-CD3 monoclonal antibodies (mAbs) modify human immune responses in type 1 diabetes (T1DM) is not known. We prepared a panel of Class I HLA-A2.1 tetramers with peptides from diabetes-associated antigens and studied the frequency and phenotype of the cells in patients with T1DM and blood donors and in patients treated with anti-CD3 mAb (Teplizumab). More patients with T1DM showed positive staining for at least 1 tetramer using frozen and fresh samples (p<0.05). Three months following treatment with anti-CD3 mAb, the proportion of GAD65- and InsB-peptide reactive CD8+ T cells increased (p<0.05)....
Source: Clinical Immunology - October 14, 2009 Category: Allergy & Immunology Authors: Cernea S, Herold KC Tags: Clin Immunol Source Type: journals

Exposure of NK cells to intravenous immunoglobulin induces IFNgamma release and degranulation but inhibits their cytotoxic activity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mechanisms underlying the modulation of Natural Killer (NK) cell functions by intravenous immunoglobulin (IVIg) are poorly understood. Using an ex vivo whole blood assay system we demonstrate that IVIg suppresses NK cell cytotoxicity. This was paralleled by IVIg-induced degranulation of CD56(bright), CD16(positive) NK cells, reduced expression of CD16 and elevated IFNgamma release. To assess whether these findings also occur in vivo we analyzed whole blood before and after IVIg therapy of patients. Following IVIg treatment the number of NK cells in peripheral blood dropped significantly. We observed reduced CD16 ex...
Source: Clinical Immunology - October 11, 2009 Category: Allergy & Immunology Authors: Jacobi C, Claus M, Wildemann B, Wingert S, Korporal M, Römisch J, Meuer S, Watzl C, Giese T Tags: Clin Immunol Source Type: journals

Modulation of the colonic epithelial cell responses and amelioration of inflammation by CD80 blockade in TNBS colitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, CD80-CAP administration ameliorated TNBS colitis by reducing the inflammatory cell infiltration and modulating the CEC response potentially restoring mucosal tolerance. PMID: 19811954 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - October 5, 2009 Category: Allergy & Immunology Authors: Srinivasan M, Summerlin DJ Tags: Clin Immunol Source Type: journals

New insights into the pathophysiology of idiopathic nephrotic syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Corticoresistant idiopathic nephrotic syndrome (INS) is a glomerulopathy of unknown etiology whose original aspect is its recurrence after kidney transplantation in 30 to 50% of patients with end-stage renal disease. This suggests the involvement of circulating factors that would alter the glomerular filtration barrier, but whose nature remains elusive. Although a T cell immune origin has been suggested, the actual role of these cells in INS recurrence is still unclear. Here we present an 8-year-old patient with corticoresistant INS who developed a recurrence of her initial disease after kidney transplantation. Rituxim...
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Bruneau S, Dantal J Tags: Clin Immunol Source Type: journals

Is preeclampsia an autoimmune disease?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Preeclampsia is a life-threatening hypertensive disease of pregnancy. The condition is characterized by the presence of autoantibodies that activate the major angiotensin receptor, AT(1). Research conducted during the past decade has shown that these autoantibodies activate AT(1) receptors on a variety of cell types and provoke biological responses that are relevant to the pathophysiology of preeclampsia. The introduction of these autoantibodies into pregnant mice results in hypertension, proteinuria and a variety of other features of preeclampsia including small fetuses and placentas. These findings demonstrate the pa...
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Xia Y, Kellems RE Tags: Clin Immunol Source Type: journals

Selective IgA deficiency in early life: association to infections and allergic diseases during childhood.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Selective IgA deficiency in early life is quite common in Caucasian populations, but it is unclear whether it increases the risk of infections and allergic diseases during childhood. Serum IgA levels were measured in 2423 children at 4 years of age in a Swedish population based birth cohort (BAMSE). Parental questionnaires were repeatedly sent out during the child's first 8 years of life, collecting information about infections and allergic diseases. 14 children (1:173) were found to be IgA deficient at 4 years of age. These children had an increased risk of pseudocroup at year 1 (p<0.01) and food hypersensitivity a...
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Janzi M, Kull I, Sjöberg R, Wan J, Melén E, Bayat N, Ostblom E, Pan-Hammarström Q, Nilsson P, Hammarström L Tags: Clin Immunol Source Type: journals

First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Here, we describe a procedure and first-in-man clinical effects of adoptive transfer of ex vivo expanded CD4+CD25+CD127- T regulatory cells (Tregs) in the treatment of graft versus host disease (GvHD). The cells were sorted from buffy coats taken from two family donors, expanded ex vivo and transferred to respective recipients who suffered from either acute or chronic GvHD. The therapy allowed for significant alleviation of the symptoms and reduction of pharmacologic immunosuppression in the case of chronic GvHD, while in the case of grade IV acute GvHD it only transiently improved the condition, for the longest time w...
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Trzonkowski P, Bieniaszewska M, Juścińska J, Dobyszuk A, Krzystyniak A, Marek N, Myśliwska J, Hellmann A Tags: Clin Immunol Source Type: journals

Interferon-beta treatment in multiple sclerosis attenuates inflammatory gene expression through inducible activity of the phosphatase SHP-1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, interferon-beta treatment upregulates SHP-1 expression resulting in decreased transcription factor activation and inflammatory gene expression important in MS pathogenesis. PMID: 19559654 [PubMed - indexed for MEDLINE] (Source: Clinical Immunology)
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Christophi GP, Panos M, Hudson CA, Tsikkou C, Mihai C, Mejico LJ, Jubelt B, Massa PT Tags: Clin Immunol Source Type: journals

A tolerogenic peptide that induces suppressor of cytokine signaling (SOCS)-1 restores the aberrant control of IFN-gamma signaling in lupus-affected (NZB x NZW)F1 mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interferon-gamma (IFN-gamma) plays a pathogenic role in systemic lupus erythematosus (SLE). Uncontrolled IFN-gamma signaling may result from a deficiency in the negative regulator, namely, suppressor of cytokine signaling-1 (SOCS-1). We investigated the activation status of IFN-gamma signaling pathway in SLE-afflicted (New-Zealand-BlackxNew-Zealand-White)F1 mice and determined its responsiveness when treating with a tolerogenic peptide, hCDR1, which ameliorates SLE. SOCS-1 was suppressed and pSTAT1 was enhanced in spleen-derived cells from SLE-affected mice as compared with healthy controls. Treatment with hCDR1 revers...
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Sharabi A, Sthoeger ZM, Mahlab K, Lapter S, Zinger H, Mozes E Tags: Clin Immunol Source Type: journals

Galectin-9 ameliorates immune complex-induced arthritis by regulating FcgammaR expression on macrophages.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Galectin-9 up-regulated FcgammaRIIb expression of mouse peritoneal macrophages in vitro but down-regulated FcgammaRIII expression. Galectin-9-treated macrophages stimulated with immune complexes (IC) produced less TNFalpha and IL-1beta but more IL-10 than PBS-treated macrophages. Macrophage enhancing effects on IC-induced C5a and neutrophil chemotactic activity were also diminished for galectin-9-treated macrophages. In galectin-9-treated mice, the severity of IC-induced arthritis was reduced, as were pro-inflammatory cytokine levels in inflamed joints and serum C5a. FcgammaRIIb expression of macrophages from galectin-...
Source: Clinical Immunology - September 30, 2009 Category: Allergy & Immunology Authors: Arikawa T, Watanabe K, Seki M, Matsukawa A, Oomizu S, Sakata KM, Sakata A, Ueno M, Saita N, Niki T, Yamauchi A, Hirashima M Tags: Clin Immunol Source Type: journals

Estradiol targets T cell signaling pathways in human systemic lupus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differe...
Source: Clinical Immunology - September 28, 2009 Category: Allergy & Immunology Authors: Walters E, Rider V, Abdou NI, Greenwell C, Svojanovsky S, Smith P, Kimler BF Tags: Clin Immunol Source Type: journals

Molecular assessment of thymic capacities in patients with Schimke immuno-osseous dysplasia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Schimke immuno-osseous dysplasia (SIOD) is caused by SMARCAL1 deficiency and characterized by defective T-cell immunity. The immunodeficiency and the role of thymic function in SIOD patients are not clearly understood. We performed thymic evaluations by assessing T-cell receptor (TCR) diversity, rearrangement, and excision circles in family members with different disease severity carrying the same bi-allelic mutation and in a heterozygous carrier. The expression of SMARCAL1 mRNA in a normal thymic sample was measured using real-time quantitative polymerase chain reaction. Thymus functions were significantly reduced in ...
Source: Clinical Immunology - September 28, 2009 Category: Allergy & Immunology Authors: Lev A, Amariglio N, Levy Y, Spirer Z, Anikster Y, Rechavi G, Dekel B, Somech R Tags: Clin Immunol Source Type: journals

Study of thymic size and function in children and adolescents with treatment refractory systemic sclerosis eligible for immunoablative therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Following hematopoietic stem cell transplantation (HSCT), thymic reconstitution of peripheral T lymphocytes is essential to avoid a chronically immunodeficient state and disease recurrence. The purpose of this study was to determine if children and adolescents with treatment refractory SSc, awaiting HSCT, have sufficient thymic function to reconstitute T lymphocyte function after transplantation. Thirteen children with systemic scleroderma were enrolled and assessed by physical exam, chest MRI, measurement of autoantibodies, B and T cell immuno-phenotyping, and quantization of T cell receptor rearrangement excision cir...
Source: Clinical Immunology - September 27, 2009 Category: Allergy & Immunology Authors: Reiff A, Krogstad P, Moore S, Shaham B, Parkman R, Kitchen C, Weinberg K Tags: Clin Immunol Source Type: journals

Autoimmune T cell responses to antigenic peptides presented by bronchoalveolar lavage cell HLA-DR molecules in sarcoidosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The etiology of sarcoidosis remains unknown. Recently, by mass spectrometric sequencing of peptides eluted from HLA-DR molecules of bronchoalveolar lavage (BAL) cells from DRB10301(pos) patients, we identified potential self-antigens in sarcoidosis. The aim of the present study was to investigate the capacity of selected peptides to stimulate lung and blood T cells of sarcoidosis patients using an interferon-gamma ELISPOT assay. In peripheral blood, there were strong T cell responses to a peptide derived from the cytoskeletal protein vimentin in 6 out of 11 DRB10301(pos) patients with active disease but not in patients...
Source: Clinical Immunology - September 25, 2009 Category: Allergy & Immunology Authors: Wahlström J, Dengjel J, Winqvist O, Targoff I, Persson B, Duyar H, Rammensee HG, Eklund A, Weissert R, Grunewald J Tags: Clin Immunol Source Type: journals

Cutaneous T cell lymphoma and graft-versus-host disease: A comparison of in vivo effects of extracorporeal photochemotherapy on Foxp3+ regulatory T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Extracorporeal photochemotherapy (ECP) is a well established treatment for both cutaneous T cell lymphoma (CTCL) and graft-versus-host disease (GVHD). However, the general effector mechanism is not fully settled. Twenty-four patients with CTCL and 14 patients with GVHD were included to assess the relative numbers of regulatory T cells (Treg) and any change in the serum cytokine profile during 6 months of ECP therapy. The relative amount of Treg cells was twice as high in CTCL compared to GVHD and healthy controls. TGF-beta was on average three times higher in GVHD than in CTCL. Both patient groups had a small but signi...
Source: Clinical Immunology - September 18, 2009 Category: Allergy & Immunology Authors: Rao V, Saunes M, Jørstad S, Moen T Tags: Clin Immunol Source Type: journals

Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
T cells play central roles in liver diseases, but the regulatory mechanism by cytokine signaling is not well understood. In the present study, we explored the role of SOCS3 in T cells in concanavalin A (ConA)-induced hepatitis. Mice with T-cell-specific overexpression of SOCS3 (SOCS3-cTg) showed reduced hepatic damage and improved mice survival relative to the control, an event that was associated with decreased apoptotic signals Fas and pStat1. Expression of Th1-cytokines/chemokines was decreased in SOCS3-cTg liver with reduced expression of T-bet, a Th1-transcription factor. Flow cytometric analysis of the liver lymp...
Source: Clinical Immunology - September 16, 2009 Category: Allergy & Immunology Authors: Fushimi S, Ogino T, Hara J, Takahata T, Wakabayashi H, Watanabe H, Arashima Y, Kubo M, Matsukawa A Tags: Clin Immunol Source Type: journals

The CD4(+)CD25(bright) regulatory T cells and CTLA-4 expression in peripheral and decidual lymphocytes are down-regulated in human miscarriage.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we showed that CD4(+)CD25(bright) T cells significantly increased in the peripheral of normal pregnancy compared to that of non-pregnancy. The proportions of CD4(+)CD25(bright) T cells in both peripheral blood and deciduas were significantly lower in miscarriage than that of normal pregnancy. CD4(+)CD25(bright) T cells were characterized by high-level FoxP3 expression and low-level CD69 expression. An increase in the CD28 mRNA expression was accompanied by a decrease in the CTLA-4 mRNA expression in decidual tissues from human miscarriage. The ratios of CTLA-4(+)/CD28(+) in miscarriage were significantly low...
Source: Clinical Immunology - September 15, 2009 Category: Allergy & Immunology Authors: Jin LP, Chen QY, Zhang T, Guo PF, Li DJ Tags: Clin Immunol Source Type: journals

Behavior of non-classical soluble HLA class G antigens in human immunodeficiency virus 1-infected patients before and after HAART: Comparison with classical soluble HLA-A, -B, -C antigens and potential role in immune-reconstitution.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we measured the levels of soluble HLA-G (sHLA-G) antigens in a cohort of HIV-infected patients before and during HAART. sHLA-G and sHLA-A, -B, -C levels were significantly elevated in HIV-infected subjects as compared with controls before antiretroviral treatment and significantly decreased after 36 months of HAART. sHLA-G levels were correlated with sHLA-A, -B, -C levels, the decrease of plasma HIV-RNA level, the increase of CD4+ T-lymphocyte number and the decrease of CD8+ T-lymphocyte number. These results suggest that the measurement of sHLA-G and sHLA-A, -B, -C antigen serum levels might represent a use...
Source: Clinical Immunology - September 15, 2009 Category: Allergy & Immunology Authors: Murdaca G, Contini P, Setti M, Cagnati P, Lantieri F, Indiveri F, Puppo F Tags: Clin Immunol Source Type: journals

Autologous MUC1-specific Th1 effector cell immunotherapy induces differential levels of systemic TReg cell subpopulations that result in increased ovarian cancer patient survival.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Adoptive T cell immunotherapy using autologous lymphocytes is a viable treatment for patients with cancer and requires participation of Ag-specific CD4 and CD8 T cells. Here, we assessed the immunotherapeutic effects of autologous MUC1 peptide-stimulated CD4(+) effector cells following adoptive transfer in patients with ovarian cancer. Using MUC1 peptide and IL-2 for ex vivo CD4(+)/Th1 effector cell generation, we show that three monthly treatment cycles of peripheral blood T cell restimulation and intraperitoneal re-infusion selectively modulated endogenous T cell-mediated immune responses that correlated with diminis...
Source: Clinical Immunology - September 14, 2009 Category: Allergy & Immunology Authors: Dobrzanski MJ, Rewers-Felkins KA, Quinlin IS, Samad KA, Phillips CA, Robinson W, Dobrzanski DJ, Wright SE Tags: Clin Immunol Source Type: journals

Down-regulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined the mRNA expression levels of TIPE2 and myxoma resistance protein (MX) 1 (one of type I interferon inducible genes) in peripheral blood mononuclear cells (PBMC) from 39 SLE patients and 35 healthy controls by real-time reverse transcription-polymerase chain reaction analysis (RT-PCR). The TIPE2 mRNA expression was significantly down-regulated in SLE patients compared with healthy controls (P=0.0004), while the MX1 mRNA expression was increased in SLE patients compared with healthy controls (P=0.0031). Furthermore, the TIPE2 mRNA expression levels negatively correlate with the SLE disease activity index (SLEDAI)...
Source: Clinical Immunology - September 10, 2009 Category: Allergy & Immunology Authors: Li D, Song L, Fan Y, Li X, Li Y, Chen J, Zhu F, Guo C, Shi Y, Zhang L Tags: Clin Immunol Source Type: journals

Low level natural antibodies against phosphorylcholine: A novel risk marker and potential mechanism in atherosclerosis and cardiovascular disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atherosclerosis is an inflammatory condition characterised by an abundance of activated immunocompetent cells in plaques which cause cardiovascular disease (CVD) when they rupture. Oxidized forms of low density lipoprotein (OxLDL) are a major constituent of atherosclerotic plaques and have proinflammatory effects, making oxLDL a candidate factor promoting atherosclerosis. In previous studies we and others demonstrated that platelet-activating factor (PAF)-like lipids in oxLDL may cause oxLDL-induced immune-stimulatory effects. A common denominator is phosphorylcholine (PC), a hapten-like epitope which is exposed on OxL...
Source: Clinical Immunology - September 9, 2009 Category: Allergy & Immunology Authors: Frostegård J Tags: Clin Immunol Source Type: journals

Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report a 4-month-old female who presented with failure to thrive, normocytic anemia, Pneumocystis jirovecii pneumonia and systemic cytomegalovirus infection. Immunological evaluation revealed hypogammaglobulinemia, absent antibody responses, and lack of mitogen-induced lymphocyte proliferative responses. However, the absolute number and distribution of lymphocyte subsets, including naïve T cells and recent thymic emigrants, were normal, arguing against primary SCID. Serum and cerebrospinal fluid folate levels were undetectable. A homozygous 1082-1G>A mutation of the PCFT gene was found, resulting in skipping of ...
Source: Clinical Immunology - September 7, 2009 Category: Allergy & Immunology Authors: Borzutzky A, Crompton B, Bergmann AK, Giliani S, Baxi S, Martin M, Neufeld EJ, Notarangelo LD Tags: Clin Immunol Source Type: journals

Innate immune signals in atherosclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atherosclerosis is a chronic disease characterised by lipid retention and inflammation in the arterial intima. Innate immune mechanisms are central to atherogenesis, involving activation of pattern-recognition receptors (PRRs) and induction of inflammatory processes. In a complex tissue, such as the atherosclerotic lesion, innate signals can originate from several sources and promote atherogenesis through ligation of PRRs. The receptors recognise conserved molecular patterns on pathogens and endogenous products of tissue injury and inflammation. Activation of PRRs might affect several aspects of atherosclerosis by acti...
Source: Clinical Immunology - September 7, 2009 Category: Allergy & Immunology Authors: Lundberg AM, Hansson GK Tags: Clin Immunol Source Type: journals

Differential susceptibility to apoptosis of CD4+T cells expressing CCR5 and CXCR3 in patients with MS.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We aimed to evaluate differences in the susceptibility to apoptosis of CD4+CCR5+ and CD4+CXCR3+T cells between MS patients (N=41) and controls (N=15) 6 days after activation of peripheral blood cells with anti-CD3 antibodies and 24 h following stimulation with anti-Fas antibodies. Susceptibility to anti-CD3 induced activation-induced cell death (AICD) and Fas-mediated apoptosis was selectively increased in CD4+CCR5+T cells compared with CD4+CCR5- and CD4+CXCR3-/+T cells. Compared with controls, CD4+CCR5+T cells from patients with primary progressive MS (PPMS) were more resistant to anti-CD3-induced AICD and anti-Fas-in...
Source: Clinical Immunology - September 6, 2009 Category: Allergy & Immunology Authors: Julià E, Edo MC, Horga A, Montalban X, Comabella M Tags: Clin Immunol Source Type: journals

The role of resistin as a regulator of inflammation: Implications for various human pathologies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Resistin was originally described as an adipocyte-secreted peptide that induced insulin resistance in rodents. Increasing evidence indicates its important regulatory roles in various biological processes, including several inflammatory diseases. Further studies have shown that resistin in humans, in contrast to its production by adipocytes in mice, is synthesized predominantly by mononuclear cells both within and outside adipose tissue. Possible roles for resistin in obesity-related subclinical inflammation, atherosclerosis and cardiovascular disease, non-alcoholic fatty liver disease, rheumatic diseases, malignant tum...
Source: Clinical Immunology - September 6, 2009 Category: Allergy & Immunology Authors: Filková M, Haluzík M, Gay S, Senolt L Tags: Clin Immunol Source Type: journals

AA28-67 domain within MyD88 suppresses c-myc activity and expression to regulate differentiation and function of dendritic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mechanism by which c-myc expression in undifferentiated cells rapidly declines following induction of differentiation is poorly characterized. We demonstrate here that MyD88, which can activate NF-kappaB and MAPK, also suppresses c-myc activity and expression. The aa 28-67 domain, a highly conserved region within MyD88, plays a critical role in the MyD88-mediated inhibition. Indeed, deletion of the aa 28-67 domain (MyD88Delta28-67) or mutation of the highly conserved amino acid residue phenylalanine (aa 36) to aspartic acid (MyD88DeltaF36D) significantly promoted c-myc activity and expression. Additionally, we foun...
Source: Clinical Immunology - September 6, 2009 Category: Allergy & Immunology Authors: Zhang Z, Zeng B, Jiao G, Li Y, Liu Y, Zhang Y, Yang R Tags: Clin Immunol Source Type: journals

Fulfilling the promise of immunology for human health.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Authors: PMID: 19740708 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - September 6, 2009 Category: Allergy & Immunology Tags: Clin Immunol Source Type: journals

Simultaneous quantitative analysis of FcgammaRI (CD64) and CR1 (CD35) on neutrophils in distinguishing between bacterial infections, viral infections, and inflammatory diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A flow cytometric quantitative analysis of receptors on neutrophils can be exploited in distinguishing between inflammatory and infectious diseases. In this prospective comparative study, simultaneous quantitative analysis of CD64 and CD35 on peripheral blood neutrophils was performed in febrile patients in order to differentiate between bacterial infections (n=89), viral infections (n=46), and inflammatory diseases (n=21). The patient data was compared to 60 healthy controls. We could divide patients into three groups depending on how they express CD35 and CD64 on neutrophils: (1) patients with a high probability of v...
Source: Clinical Immunology - September 3, 2009 Category: Allergy & Immunology Authors: Jalava-Karvinen P, Hohenthal U, Laitinen I, Kotilainen P, Rajamäki A, Nikoskelainen J, Lilius EM, Nuutila J Tags: Clin Immunol Source Type: journals

Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSION: Our findings derived from a homogenous southern European population with low incidence of T1D suggest that FokI, BsmI, ApaI, and TaqI polymorphisms of the VDR gene are associated with T1D prevalence. PMID: 19734102 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - September 3, 2009 Category: Allergy & Immunology Authors: Panierakis C, Goulielmos G, Mamoulakis D, Petraki E, Papavasiliou E, Galanakis E Tags: Clin Immunol Source Type: journals

Monitoring immunosuppression with measures of NFAT decreases cancer incidence.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a 67-year-old patient with a history of recurrent non-melanoma skin cancer. After adjustment of immunosuppressive therapy under close pharmacodynamic control, the development of new malignant lesions could be prevented. The availability of a quantitative, quick laboratory test for an assessment of the individual functional activity of immunocompetent cells that are crucial for transplant rejection, defense against viral infection, and tumor surveillance along with the ability to adjust doses of immunosuppressive agents such that patients are largely protected against malignant disease and/or viral infection are ...
Source: Clinical Immunology - August 31, 2009 Category: Allergy & Immunology Authors: Giese T, Sommerer C, Zeier M, Meuer S Tags: Clin Immunol Source Type: journals

Breaking old paradigms: Th17 cells in autoimmune arthritis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Aberrant helper T cell activation has been implicated in the pathogenesis of an array of autoimmune diseases. In this review, we summarize evidence that suggests the involvement of a novel T cell subset, the Th17 lineage, in rheumatoid arthritis. In particular, we focus on the role of Th17 cells in inducing and perpetuating the chronic inflammation, cartilage damage, and bone erosion that are hallmark phases of joint destruction and consider current and emerging therapies that seek to disrupt the inflammatory Th17 network and shift the immune system back towards homeostasis. PMID: 19403336 [PubMed - indexed for MED...
Source: Clinical Immunology - August 31, 2009 Category: Allergy & Immunology Authors: Peck A, Mellins ED Tags: Clin Immunol Source Type: journals

Frequency of gC1qR+CD4+ T cells increases during acute hepatitis C virus infection and remains elevated in patients with chronic infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD4+ T cell responses are impaired in chronic HCV infection. To determine factor(s) involved in CD4+ T cell dysregulation, we examined the effect of extracellular core on the alteration of CD4+ T cell responses and the cell surface level of core-binding protein, gC1qR on CD4+ T cells from acute HCV patients with resolved and chronic infection. During the acute phase of infection, the frequency of gC1qR+CD4+ T cells increased in both resolved and chronic HCV infection compared to healthy controls. Notably, 6 months later, the frequency of gC1qR+CD4+ T cells maintained elevated in chronic patients compared to that in res...
Source: Clinical Immunology - August 31, 2009 Category: Allergy & Immunology Authors: Cummings KL, Rosen HR, Hahn YS Tags: Clin Immunol Source Type: journals

Cultured peripheral blood mast cells from chronic idiopathic urticaria patients spontaneously degranulate upon IgE sensitization: Relationship to expression of Syk and SHIP-2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recently, signaling changes in the FcvarepsilonRI pathway involving inositol lipid phosphatases have been identified in the basophils of chronic idiopathic urticaria (CIU) subjects. Based on the profile of basophil FcvarepsilonRI-mediated histamine degranulation, we have segregated CIU subjects into two groups, CIU Responder (CIU R) or CIU Nonresponder (CIU NR). In the present study, we compared expression of SHIP-1, SHIP-2, and Syk protein to histamine release (HR) from mast cells (MC) cultured from the peripheral blood of CIU R, CIU NR, and normal subjects. The MC of CIU R donors contained significantly increased Syk...
Source: Clinical Immunology - August 31, 2009 Category: Allergy & Immunology Authors: Saini SS, Paterniti M, Vasagar K, Gibbons SP, Sterba PM, Vonakis BM Tags: Clin Immunol Source Type: journals

Changes in autoreactive T cell avidity during type 1 diabetes development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The activation threshold for antigen-specific T cell responses is dependent on the avidity of the trimolecular interaction between TCR, antigen, and MHC. We compared CD4+ T cell avidities for the diabetes-associated autoantigen glutamic acid decarboxylase 555-567 (GAD 555) among serial samples from autoantibody-positive subjects at high risk of progression to type 1 diabetes (T1D). T cells from three at-risk subjects demonstrated significant avidity increases (p<0.05 by F test) over time. This avidity shift correlated with the outgrowth of T cells expressing TCR BV 9, 15, 17 or 20 that demonstrated higher GAD 555 te...
Source: Clinical Immunology - August 31, 2009 Category: Allergy & Immunology Authors: Standifer NE, Burwell EA, Gersuk VH, Greenbaum CJ, Nepom GT Tags: Clin Immunol Source Type: journals