Autoimmune Diseases最新文献

{"title":"Exploring T cell reactivity to gliadin in young children with newly diagnosed celiac disease.","authors":"Edwin Liu,&nbsp;Kristen McDaniel,&nbsp;Stephanie Case,&nbsp;Liping Yu,&nbsp;Bernd Gerhartz,&nbsp;Nils Ostermann,&nbsp;Gabriela Fankhauser,&nbsp;Valerie Hungerford,&nbsp;Chao Zou,&nbsp;Marcel Luyten,&nbsp;Katherine J Seidl,&nbsp;Aaron W Michels","doi":"10.1155/2014/927190","DOIUrl":"https://doi.org/10.1155/2014/927190","url":null,"abstract":"<p><p>Class II major histocompatibility molecules confer disease risk in Celiac disease (CD) by presenting gliadin peptides to CD4 T cells in the small intestine. Deamidation of gliadin peptides by tissue transglutaminase creates immunogenic peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4 T cells. Detecting gliadin specific T cell responses from the peripheral blood has been challenging due to low circulating frequencies and heterogeneity in response to gliadin epitopes. We investigated the peripheral T cell responses to alpha and gamma gliadin epitopes in young children with newly diagnosed and untreated CD. Using peptide/MHC recombinant protein constructs, we are able to robustly stimulate CD4 T cell clones previously derived from intestinal biopsies of CD patients. These recombinant proteins and a panel of α- and γ-gliadin peptides were used to assess T cell responses from the peripheral blood. Proliferation assays using peripheral blood mononuclear cells revealed more CD4 T cell responses to α-gliadin than γ-gliadin peptides with a single deamidated α-gliadin peptide able to identify 60% of CD children. We conclude that it is possible to detect T cell responses without a gluten challenge or in vitro stimulus other than antigen, when measuring proliferative responses. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"927190"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/927190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32255328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirin for prevention of preeclampsia in lupus pregnancy.","authors":"Amelie M Schramm,&nbsp;Megan E B Clowse","doi":"10.1155/2014/920467","DOIUrl":"https://doi.org/10.1155/2014/920467","url":null,"abstract":"<p><p>Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"920467"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/920467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32300753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celiac disease in adult patients: specific autoantibodies in the diagnosis, monitoring, and screening.","authors":"Evagelia Trigoni,&nbsp;Alexandra Tsirogianni,&nbsp;Elena Pipi,&nbsp;Gerassimos Mantzaris,&nbsp;Chryssa Papasteriades","doi":"10.1155/2014/623514","DOIUrl":"https://doi.org/10.1155/2014/623514","url":null,"abstract":"<p><p>The increasing prevalence of celiac disease (CD), especially in adults, its atypical clinical presentation, and the strict, lifelong adherence to gluten-free diet (GFD) as the only option for healthy state create an imperative need for noninvasive methods that can effectively diagnose CD and monitor GFD. Aim. Evaluation of anti-endomysium (EmA) and anti-tissue transglutaminase IgA (tTG-A) antibodies in CD diagnosis, GFD monitoring, and first degree relatives screening in CD adult patients. Methods. 70 newly diagnosed Greek adult patients, 70 controls, and 47 first degree relatives were tested for the presence of EmA and tTG-A. The CD patients were monitored during a 3-year period. Results. EmA predictive ability for CD diagnosis was slightly better compared to tTG-A (P = 0.043). EmA could assess compliance with GFD already from the beginning of the diet, while both EmA and tTG-A had an equal ability to discriminate between strictly and partially compliant patients after the first semester and so on. Screening of first degree relatives resulted in the identification of 2 undiagnosed CD cases. Conclusions. Both EmA and tTG-A are suitable markers in the CD diagnosis, in the screening of CD among first degree relatives, having also an equal performance in the long term monitoring. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"623514"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/623514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32322662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elements of the B cell signalosome are differentially affected by mercury intoxication.","authors":"Randall F Gill,&nbsp;Michael J McCabe,&nbsp;Allen J Rosenspire","doi":"10.1155/2014/239358","DOIUrl":"https://doi.org/10.1155/2014/239358","url":null,"abstract":"<p><p>It has been suggested that environmental exposures to mercury contribute to autoimmune disease. Disruption of BCR signaling is associated with failure of central tolerance and autoimmunity, and we have previously shown that low levels of Hg(2+) interfere with BCR signaling. In this report we have employed multiparametric phosphoflow cytometry, as well as a novel generalization of the Overton algorithm from one- to two-dimensional unimodal distributions to simultaneously monitor the effect of low level Hg(2+) intoxication on activation of ERK and several upstream elements of the BCR signaling pathway in WEHI-231 B cells. We have found that, after exposure to low levels of Hg(2+), only about a third of the cells are sensitive to the metal. For those cells which are sensitive, we confirm our earlier work that activation of ERK is attenuated but now report that Hg(2+) has little upstream effect on the Btk tyrosine kinase. On the other hand, we find that signaling upstream through the Syk tyrosine kinase is actually augmented, as is upstream activation of the B cell signalosome scaffolding protein BLNK. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"239358"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/239358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32379778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmunity and the gut.","authors":"Andrew W Campbell","doi":"10.1155/2014/152428","DOIUrl":"https://doi.org/10.1155/2014/152428","url":null,"abstract":"<p><p>Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"152428"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/152428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32399254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in neuroimmunology: from bench to bedside.","authors":"Cristoforo Comi,&nbsp;Umberto Dianzani,&nbsp;Filippo Martinelli Boneschi,&nbsp;Daniel L Menkes","doi":"10.1155/2014/812847","DOIUrl":"https://doi.org/10.1155/2014/812847","url":null,"abstract":"The understanding of the interactions between the immune and the nervous systems and the resultant therapeutic implications has expanded significantly in the last decade [1]. There have been significant developments in the field of neuroimmunology as new antibody-mediated disorders have been described and involvement of the immune system in the pathogenesis of neurodegenerative diseases has been established [2, 3]. These discoveries have led to novel and effective treatments, which have broadened our therapeutic options regarding neuroimmune disorders [4, 5]. \u0000 \u0000The goal of this special issue was to address the translational aspects of neuroimmunology, “from bench to bedside,” in order to update clinicians on basic research discoveries that will have therapeutic clinical efficacy. Moreover, there was an emphasis on conditions that have undergone a systematic nosographic characterization which have resulted in therapeutic approaches with greater specificity. In this context, the paper entitled “Immunotherapy of neuromyelitis optica” provides a framework for understanding an antibody-mediated central nervous system demyelinating disease that has a different pathophysiology than multiple sclerosis (MS). This distinction is important as NMO responds to different immunomodulating agents than does MS. \u0000 \u0000The spectrum of pediatric MS has also been the focus of extensive nosographic revision in recent years, and diagnostic criteria have been recently revised by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) [6]. The paper “Pediatric multiple sclerosis: current concepts and consensus definitions” offers a careful update on risk factors, clinical manifestations, diagnostic procedures, prognostic implications, and treatment of this increasingly frequent form of MS. \u0000 \u0000MS is a salient neuroimmunological disease for which the “bench to bedside approach” has provided the greatest therapeutic advances. Although there are more treatments for MS, the study of novel and less explored molecular pathways ought to provide relevant alternative targets. This concept is well expressed in the paper entitled “Current understanding on the role of standard- and immuno-proteasomes in inflammatory/immunological pathways of Multiple Sclerosis,” in which the authors describe the current knowledge on the potential role of proteasomes in MS and discuss the pro et contra of possible therapies for MS targeting proteasome isoforms. \u0000 \u0000Immune mediated diseases of the peripheral nervous system (PNS) are less studied than their “central” counterparts [7]. Nonetheless, important advances in both pathogenesis and treatment of inflammatory demyelinating neuropathies have been extensively evaluated in the articles authored by J. B. Weiner and P. Ripellino et al. The first publication entitled “An update in Guillain-Barre Syndrome” provides a comprehensive discussion of the current state of knowledge on acute inflammatory neuropathies from diagnosis to treatment. The se","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"812847"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/812847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32158476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of anti-nuclear antibody quantification using automated enzyme immunoassays and immunofluorescence assays.","authors":"Renata Baronaite,&nbsp;Merete Engelhart,&nbsp;Troels Mørk Hansen,&nbsp;Gorm Thamsborg,&nbsp;Hanne Slott Jensen,&nbsp;Steen Stender,&nbsp;Pal Bela Szecsi","doi":"10.1155/2014/534759","DOIUrl":"https://doi.org/10.1155/2014/534759","url":null,"abstract":"<p><p>Anti-nuclear antibodies (ANA) have traditionally been evaluated using indirect fluorescence assays (IFA) with HEp-2 cells. Quantitative immunoassays (EIA) have replaced the use of HEp-2 cells in some laboratories. Here, we evaluated ANA in 400 consecutive and unselected routinely referred patients using IFA and automated EIA techniques. The IFA results generated by two independent laboratories were compared with the EIA results from antibodies against double-stranded DNA (dsDNA), from ANA screening, and from tests of the seven included subantigens. The final IFA and EIA results for 386 unique patients were compared. The majority of the results were the same between the two methods (n = 325, 84%); however, 8% (n = 30) yielded equivocal results (equivocal-negative and equivocal-positive) and 8% (n = 31) yielded divergent results (positive-negative). The results showed fairly good agreement, with Cohen's kappa value of 0.30 (95% confidence interval (CI) = 0.14-0.46), which decreased to 0.23 (95% CI = 0.06-0.40) when the results for dsDNA were omitted. The EIA method was less reliable for assessing nuclear and speckled reactivity patterns, whereas the IFA method presented difficulties detecting dsDNA and Ro activity. The automated EIA method was performed in a similar way to the conventional IFA method using HEp-2 cells; thus, automated EIA may be used as a screening test. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"534759"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/534759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32174769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic lupus erythematosus 2014.","authors":"Juan-Manuel Anaya,&nbsp;Yehuda Shoenfeld,&nbsp;Ricard Cervera","doi":"10.1155/2014/274323","DOIUrl":"https://doi.org/10.1155/2014/274323","url":null,"abstract":"Systemic lupus erythematosus (SLE, lupus) is the prototype of systemic autoimmune disease (AD). Immune system activation in SLE is characterized by exaggerated B-cell and T-cell responses and loss of immune tolerance against self-antigens. Production and defective elimination of antibodies, circulation and tissue deposition of immune complexes, and complement and cytokine activation contribute to clinical manifestations that range from fatigue and joint pain to severe, life-threatening organ damage [1]. In this special issue, nine papers were selected covering important topics of the disease from B lymphocytes (e.g., autoantibodies and B-cell depletion therapy), immunosenescence, and genetics to disease complications such as cardiovascular disease (CVD), preeclampsia, fatigue, and depression. B lymphocytes are the effectors of humoral immunity, providing defense from pathogens through different functions including antibody production. In the context of ADs, B lymphocytes play an essential role by not only producing autoantibodies but also functioning as antigen presenting cells and as a source of cytokines as pointed out by G. J. Tobon and colleagues, who reviewed the functions of B lymphocytes in autoimmunity and ADs with a special focus on their abnormalities in SLE. We recognize today that disease manifestations are determined by the diversity of autoantibodies appearing in SLE [2, 3]. This explains the different clinical presentations within individuals with SLE. In this issue, E. Cozzani and colleagues reviewed the most important autoantibodies in SLE and their correlation between immunopathological features and clinical aspects. Recommendations for determining anti-nuclear antibodies, anti-double stranded DNA antibodies, specific antibodies, and validation of methods have been published elsewhere [4]. Given that autoantibody production is the hallmark of SLE, it is not surprising that B-cell depletion therapy is a promising therapeutic option in the management of SLE. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has been used off-license in the management of severe refractory SLE since 2002. In this special issue, F. Bonilla-Abadia and colleagues report the results of a retrospective and descriptive observational study of patients with SLE refractory to conventional treatment who were treated with RTX as remission induction therapy and maintenance. They observed a significant reduction in the conventional immunosuppressive drug dose and the number of relapses of disease suggesting that RTX could be effective and safe in patients with SLE refractory to conventional therapy. An important matter about SLE for 2014 will be the progress and even release of results of the ongoing trials with the new biological therapies including epratuzumab, a humanized anti-CD22 monoclonal antibody, and subcutaneous belimumab, a human monoclonal antibody that inhibits B-lymphocyte stimulator, as well as the investigator-in","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"274323"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/274323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32303184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update in guillain-barré syndrome.","authors":"J B Winer","doi":"10.1155/2014/793024","DOIUrl":"https://doi.org/10.1155/2014/793024","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) was first described in 1916 (Guillain G, 1916) and is approaching its 100th anniversary. Our knowledge of the syndrome has hugely expanded since that time. Once originally considered to be only demyelinating in pathology we now recognise both axonal and demyelinating subtypes. Numerous triggering or antecedent events including infections are recognised and GBS is considered an immunological response to these. GBS is now considered to be a clinical syndrome of an acute inflammatory neuropathy encompassing a number of subtypes with evidence of different immunological mechanisms. Some of these are clearly understood while others remain to be fully elucidated. Complement fixing antibodies against peripheral nerve gangliosides alone and in combination are increasingly recognised as an important mechanism of nerve damage. New antibodies against other nerve antigens such as neurofascin have been recently described. Research databases have been set up to look at factors associated with prognosis and the influence of intravenous immunoglobulin (IvIg) pharmacokinetics in therapy. Exciting new studies are in progress to examine a possible role for complement inhibition in the treatment of the syndrome. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"793024"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/793024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32101941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mercury, autoimmunity, and environmental factors on cheyenne river sioux tribal lands.","authors":"Jennifer Ong,&nbsp;Esther Erdei,&nbsp;Robert L Rubin,&nbsp;Curtis Miller,&nbsp;Carlyle Ducheneaux,&nbsp;Marcia O'Leary,&nbsp;Bernadette Pacheco,&nbsp;Michael Mahler,&nbsp;Patricia Nez Henderson,&nbsp;K Michael Pollard,&nbsp;Johnnye L Lewis","doi":"10.1155/2014/325461","DOIUrl":"https://doi.org/10.1155/2014/325461","url":null,"abstract":"<p><p>Mercury (Hg), shown to induce autoimmune disease in rodents, is a ubiquitous toxicant throughout Cheyenne River Sioux Tribe (CRST) lands. CRST members may be exposed to Hg through fish consumption (FC), an important component of native culture that may supplement household subsistence. Our goals were to ascertain whether total blood Hg levels (THg) reflect Hg exposure through FC and smoking, and determine whether THg is associated with the presence of anti-nuclear antibody (ANA) and specific autoantibodies (sAuAb). We recruited 75 participants who regularly consume fish from CRST waters. Hg exposure through FC and smoking were assessed via questionnaires. Whole blood samples were collected from participants, and THg was measured using ICP-MS. ANA and sAuAb in serum were modeled using demographic and exposure information as predictors. Female gender, age, and FC were significant predictors of THg and sAuAb; self-reported smoking was not. 31% of participants tested positive for ANA ≥ 2+. Although ANA was not significantly associated with Hg, the interactions of gender with Hg and proximity to arsenic deposits were statistically significant (P < 0.05). FC resulted in a detectable body burden of Hg, but THg alone did not correlate with the presence of ANA or sAuAb in this population. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"325461"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/325461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32372644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}