Autoimmune Diseases The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Gender and Ethnicity Based Differences in Clinical and Laboratory Features of Myasthenia Gravis Sun, 14 Jun 2015 06:32:14 +0000 Background. Previous reports describe ethnicity based differences in clinical and laboratory features between Caucasians and African Americans with myasthenia gravis. However, it is not known whether these findings apply to other ethnicities. Methods. Retrospective analysis of all patients treated for myasthenia gravis during a three-year period at a community based medical center. Results. A total of 44 patients were included, including 19 of Hispanic, 16 of African American, 6 of Caucasian, and 3 of Asian ethnicities. Female gender was more common among those with Hispanic, Asian, and African American ethnicities compared to Caucasian ethnicity (). Anti-acetylcholine receptor antibody subtypes demonstrated no significant ethnicity based differences in either generalized or ocular myasthenia gravis. A trend was noted towards greater frequency of blocking antibodies among Hispanics (52.6%) compared to African American (37.5%) and Caucasian (33.3%) patients (). Generalized but not ocular myasthenia patients showed greater frequency of anti-muscle specific kinase antibodies in Asians and Hispanics compared to African Americans and Caucasians (). Conclusions. The results of this study support the existence of ethnicity based differences in clinical and laboratory features of myasthenia gravis. Further study of genetic factors influencing clinical features of myasthenia gravis is indicated. Fawzi Abukhalil, Bijal Mehta, Erin Saito, Sejal Mehta, and Aaron McMurtray Copyright © 2015 Fawzi Abukhalil et al. All rights reserved. Slipping through the Cracks: Linking Low Immune Function and Intestinal Bacterial Imbalance to the Etiology of Rheumatoid Arthritis Thu, 12 Mar 2015 12:47:42 +0000 Autoimmune diseases (ADs) are considered to be caused by the host immune system which attacks and destroys its own tissue by mistake. A widely accepted hypothesis to explain the pathogenic mechanism of ADs is “molecular mimicry,” which states that antibodies against an infectious agent cross-react with a self-antigen sharing an identical or similar antigenic epitope. However, this hypothesis was most likely established based on misleading antibody assay data largely influenced by intense false positive reactions involved in immunoassay systems. Thus reinvestigation of this hypothesis using an appropriate blocking agent capable of eliminating all types of nonspecific reactions and proper assay design is strongly encouraged. In this review, we discuss the possibility that low immune function may be the fundamental, common defect in ADs, which increases the susceptibility to potential disease causative pathogens located in the gastrointestinal tract (GI), such as bacteria and their components or dietary components. In addition to these exogenous agents, aberrations in the host’s physical condition may disrupt the host defense system, which is tightly orchestrated by “immune function,” “mucosal barrier function,” and “intestinal bacterial balance.” These disturbances may initiate a downward spiral, which can lead to chronic health problems that will evolve to an autoimmune disorder. Kuniaki Terato, Christopher T. Do, and Hiroshi Shionoya Copyright © 2015 Kuniaki Terato et al. All rights reserved. Environmental Triggers and Autoimmunity Wed, 24 Dec 2014 09:20:21 +0000 Aristo Vojdani, K. Michael Pollard, and Andrew W. Campbell Copyright © 2014 Aristo Vojdani et al. All rights reserved. Intravenous Immunoglobulin Treatment in Chronic Neurological Diseases: Do We Have Maintenance Dose Right? Thu, 18 Dec 2014 00:10:36 +0000 Objectives. We tried to define, on individual basis, minimal effective maintenance dose of intravenous immunoglobulins (IVIG) in 26 patients with chronic neurological conditions requiring long-term IVIG treatment. Methods. Clinical criteria were reviewed in individual cases (Phase 1) followed by titration phase (Phase 2, 12 months) and posttitration/follow-up phase (Phase 3, 3 months). Objective neurological examination and patient self-reports were used for clinical follow-up. Results. 69.2% of patients reported condition as stable, 26.9% as better, and 3.9% as mildly worse. Original mean monthly dose was 1 g/kg; over the period of 12 months we reduced dose of IVIG to mean dose 0.67 g/kg (range 0.3–2.5 g/kg, which meant reduction by 36.4%. We identified 4 nonresponders and diagnosis in one case was reclassified to degenerative disease. In follow-up phase we reduced dose further to 0.60 g/kg. Cumulative monthly dose dropped from 2040 g to 1298 g and to 991 g, respectively. Financial expenses were reduced significantly (by −36.4% during titration phase and by −51.4% during follow-up phase) (comparing with baseline) . Conclusion. Individual dose titration leads to significant maintenance IVIG dose reduction with preserved clinical efficacy. Maintenance dose below 1 g/kg (in our study around 0.7 g/kg) has acceptable risk/benefit ratio. Ondrej Dolezal Copyright © 2014 Ondrej Dolezal. All rights reserved. The Prevalence of Antinuclear Antibodies in Patients with Sarcoidosis Wed, 17 Dec 2014 12:53:26 +0000 Introduction. Sarcoidosis, which is a chronic inflammatory granulomatous disease, can mimic different rheumatologic diseases including connective tissue diseases. Antinuclear antibodies are the markers used for connective tissue diseases. Aim. To determine antinuclear antibody frequency and any possible correlation with clinical and laboratory data in sarcoidosis patients. Material and Method. Forty-two sarcoidosis patients, 45 rheumatoid arthritis patients, and 45 healthy volunteers who were followed up in rheumatology outpatient clinic were included in this study. Demographic, clinical, serological, and radiological data of all patients were recorded. Antinuclear antibodies were determined with indirect immunofluorescent method and 1/100 titration was accepted as positive. The cases that were ANA positive were evaluated with immunoblot method. Results. Average age of the 42 patients (10 males) with sarcoidosis was 45.2 (20–70 years), and average disease duration was 3.5 years. ANA positivity was detected in 12 (28.5%) patients with sarcoidosis (1/100 in 10 patients, 1/320 in two patients), in 19 of RA patients (42.2%), and in two of healthy volunteers in low titer (). In the subgroup analysis made by immunblot test, one patient had anticentromere antibody, one had anti-Ro antibody, one had anti-Scl-70 antibody, one had anti-dsDNA antibody, and eight patients were negative. The two patients who had anticentromere and anti-Scl-70 antibodies had also Sjögren’s syndrome and scleroderma diagnosis, respectively. Discussion. The prevalence of ANA in patients with sarcoidosis was found to be significantly higher than healthy control group and lower than RA patients. This result shows that ANA may have an important role in the pathogenesis of sarcoidosis and also could be important in revealing the overlap syndromes of sarcoidosis-connective tissue diseases. Further studies with larger series are necessary in this subject. Senol Kobak, Hatice Yilmaz, Fidan Sever, Arzu Duran, Nazime Sen, and Ahmet Karaarslan Copyright © 2014 Senol Kobak et al. All rights reserved. Serum Leptin Levels in Treatment-Naive Patients with Clinically Isolated Syndrome or Relapsing-Remitting Multiple Sclerosis Wed, 19 Nov 2014 09:38:22 +0000 Several studies have investigated leptin levels in patients with multiple sclerosis (MS) with somewhat conflicting results. They have all focused on patients with established relapsing-remitting (RR) MS but have not specifically looked at patients with clinically isolated syndrome (CIS) suggestive of MS, in the early stages of disease. In this study, serum leptin levels were measured in 89 treatment-naïve patients with CIS (53 patients) or RRMS (36 patients) and 73 controls searching for differences between the groups and for associations with several disease parameters. The expected significant sexual dimorphism in leptin levels (higher levels in females) was observed in both MS patients and controls. Increased leptin levels were found in female patients with RRMS compared to female controls () and female CIS patients (). Female CIS patients had comparable levels to controls. Leptin levels correlated positively to disease duration, but not to EDSS, in female patients with RRMS. The results of the present study do not indicate involvement of leptin in the early stages of MS. Normal leptin levels in patients with CIS suggest that leptin does not have a pathogenic role. The ratio leptin/BMI increases during disease course in female MS patients in a time-dependent and disability-independent manner. Maria Eleftheria Evangelopoulos, Georgios Koutsis, and Manolis Markianos Copyright © 2014 Maria Eleftheria Evangelopoulos et al. All rights reserved. Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever Wed, 22 Oct 2014 10:13:04 +0000 Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance. Ana Cristina Vanderley Oliveira, Licia Maria Henrique da Mota, Leopoldo Luiz dos Santos-Neto, Jozélio Freire De Carvalho, Iramaya Rodrigues Caldas, Olindo Assis Martins Filho, and Pedro Luis Tauil Copyright © 2014 Ana Cristina Vanderley Oliveira et al. All rights reserved. Neuroantibody Biomarkers: Links and Challenges in Environmental Neurodegeneration and Autoimmunity Mon, 23 Jun 2014 00:00:00 +0000 The majority of neurodegenerative (ND) and autoimmune diseases (AID) remain idiopathic. The contribution of environmental chemicals to the development of these disorders has become of great interest in recent years. A convergence of mechanism between of ND and AID development has also emerged. In the case of ND, including neurotoxicity, the focus of this review, work over the last two decade in the realm of biomarker development, indicates that the immune response provides a venue whereby humoral immunity, in the form of autoantibodies to nervous system specific proteins, or neuroantibodies (NAb), may provide, once validated, a sensitive high throughput surrogate biomarker of effect with the potential of predicting outcome in absence of overt neurotoxicity/neurodegeneration. In addition, NAb may prove to be a contributor to the progression of the nervous system pathology, as well as biomarker of stage and therapeutic efficacy. There is a compelling need for biomarkers of effect in light of the introduction of new chemicals, such as nanoengineered material, where potential neurotoxicity remains to be defined. Furthermore, the convergence of mechanisms associated with ND and AID draws attention to the neglected arena of angiogenesis in defining the link between environment, ND, and AID. Hassan A. N. El-Fawal Copyright © 2014 Hassan A. N. El-Fawal. All rights reserved. CD8+DR+ T-Cells and C3 Complement Serum Concentration as Potential Biomarkers in Thrombotic Antiphospholipid Syndrome Thu, 29 May 2014 13:36:14 +0000 Purpose. To assess complement factors and T lymphocyte activation subset abnormalities in patients with thrombotic antiphospholipid syndrome (APS) as potential biomarkers for development of clinical complications. Methods. We assessed C3, C4, factor B concentrations (nephelometry), complement haemolytic functional activity (CH100, radial immune diffusion), and the activation status of CD4+ and CD8+ T-cells (three-colour flow cytometry) in patients with thrombotic APS. Antiphospholipid (aPL) positive patients without APS-related clinical criteria, systemic lupus erythematosus (SLE) patients, and healthy individuals were evaluated as controls. A clinical followup was performed to assess the potential relationship between the immunological parameters and development of APS-related complications. Results. Lower concentrations of C3 and higher levels of CD8+DR+ cells were risk factors for development of APS-related complications during followup, including rethrombosis and neuropsychiatric symptoms. Patients with diagnosed thrombotic APS had significantly lower levels of C3, C4, and CH100 as well as higher percentages of activated CD4+DR+ and of CD8+DR+ T-cells than healthy controls but similar to that observed in autoimmune disease controls. Conclusion. Lower C3 and C4 complement levels and higher percentages of CD8+DR+ T-cells were observed in thrombotic APS patients. The potential role of these abnormalities as biomarkers of clinical outcome warrants further evaluation in a multicenter study. Elizabeth Sarmiento, Jonathan Dale, Mauricio Arraya, Antonio Gallego, Nallibe Lanio, Joaquin Navarro, and Javier Carbone Copyright © 2014 Elizabeth Sarmiento et al. All rights reserved. Coeliac Disease Wed, 28 May 2014 08:18:33 +0000 Raffaella Nenna, Stefano Guandalini, Alina Popp, and Kalle Kurppa Copyright © 2014 Raffaella Nenna et al. All rights reserved. Role of Autoimmune Responses in Periodontal Disease Sun, 25 May 2014 10:59:38 +0000 Periodontal diseases are characterized by localized infections and inflammatory conditions that directly affect teeth supporting structures which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidences of involvement of immunopathology have been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. This review is an attempt to throw light on the etiopathogenesis of periodontal disease highlighting the autoimmunity aspect of the etiopathogenesis involved in the initiation and progression of the disease. However, further clinical trials are required to strengthen the role of autoimmunity as a cause of periodontal disease. Soumya Nair, Mohamed Faizuddin, and Jayanthi Dharmapalan Copyright © 2014 Soumya Nair et al. All rights reserved. Autoimmunity and the Gut Tue, 13 May 2014 00:00:00 +0000 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. Andrew W. Campbell Copyright © 2014 Andrew W. Campbell. All rights reserved. Elements of the B Cell Signalosome Are Differentially Affected by Mercury Intoxication Sun, 04 May 2014 08:24:38 +0000 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 Hg2+ 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 Hg2+ 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 Hg2+, 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 Hg2+ 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. Randall F. Gill, Michael J. McCabe, and Allen J. Rosenspire Copyright © 2014 Randall F. Gill et al. All rights reserved. Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease? Wed, 30 Apr 2014 13:53:08 +0000 Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch’s membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis. Serge Camelo Copyright © 2014 Serge Camelo. All rights reserved. Autoimmunity and Asbestos Exposure Tue, 29 Apr 2014 09:25:07 +0000 Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease. Jean C. Pfau, Kinta M. Serve, and Curtis W. Noonan Copyright © 2014 Jean C. Pfau et al. All rights reserved. Mercury, Autoimmunity, and Environmental Factors on Cheyenne River Sioux Tribal Lands Thu, 24 Apr 2014 14:29:49 +0000 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 . 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. Jennifer Ong, Esther Erdei, Robert L. Rubin, Curtis Miller, Carlyle Ducheneaux, Marcia O’Leary, Bernadette Pacheco, Michael Mahler, Patricia Nez Henderson, K. Michael Pollard, and Johnnye L. Lewis Copyright © 2014 Jennifer Ong et al. All rights reserved. A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity Thu, 10 Apr 2014 07:58:27 +0000 Decay accelerating factor (DAF), a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA). Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements. David M. Cauvi, Rodney Gabriel, Dwight H. Kono, Per Hultman, and K. Michael Pollard Copyright © 2014 David M. Cauvi et al. All rights reserved. The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity Mon, 07 Apr 2014 00:00:00 +0000 Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA’s impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity. Datis Kharrazian Copyright © 2014 Datis Kharrazian. All rights reserved. Celiac Disease in Adult Patients: Specific Autoantibodies in the Diagnosis, Monitoring, and Screening Thu, 03 Apr 2014 08:48:00 +0000 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 (). 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. Evagelia Trigoni, Alexandra Tsirogianni, Elena Pipi, Gerassimos Mantzaris, and Chryssa Papasteriades Copyright © 2014 Evagelia Trigoni et al. All rights reserved. Anti-Transglutaminase 6 Antibodies in Children and Young Adults with Cerebral Palsy Wed, 02 Apr 2014 08:04:54 +0000 Objectives. We have previously reported a high prevalence of gluten-related serological markers (GRSM) in children and young adults with cerebral palsy (CP). The majority had no enteropathy to suggest coeliac disease (CD). Antibodies against transglutaminase 6 (anti-TG6) represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury resulting in CP. Materials and Methods. Sera from 96 patients with CP and 36 controls were analysed for IgA/IgG class anti-TG6 by ELISA. Results. Anti-TG6 antibodies were found in 12/96 (13%) of patients with CP compared to 2/36 (6%) in controls. The tetraplegic subgroup of CP had a significantly higher prevalence of anti-TG6 antibodies 6/17 (35%) compared to the other subgroups and controls. There was no correlation of anti-TG6 autoantibodies with seropositivity to food proteins including gliadin. Conclusions. An early brain insult and associated inflammation may predispose to future development of TG6 autoimmunity. Reidun Stenberg, Marios Hadjivassiliou, Pascale Aeschlimann, Nigel Hoggard, and Daniel Aeschlimann Copyright © 2014 Reidun Stenberg et al. All rights reserved. Systemic Lupus Erythematosus 2014 Mon, 24 Mar 2014 06:20:47 +0000 Juan-Manuel Anaya, Yehuda Shoenfeld, and Ricard Cervera Copyright © 2014 Juan-Manuel Anaya et al. All rights reserved. Aspirin for Prevention of Preeclampsia in Lupus Pregnancy Thu, 20 Mar 2014 11:10:50 +0000 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. Amelie M. Schramm and Megan E. B. Clowse Copyright © 2014 Amelie M. Schramm and Megan E. B. Clowse. All rights reserved. Role of HLA-B Alleles and Clinical Presentation of B27 Negative Spondyloarthritis Patients from Mumbai, Western India Thu, 06 Mar 2014 15:09:20 +0000 Seronegative spondyloarthritis (SpA) are variably associated with HLA-B*27 antigen. HLA-B*27 negative SpA has also been reported from different parts of the world. There is paucity of data on this entity from Indian subcontinent. We studied 100 consecutively diagnosed HLA-B27 negative spondyloarthritis patients from a tertiary care center in India. Modified New York Criteria for ankylosing spondylitis (AS) and ESSG criteria for SpA were used for diagnosing patients. HLA-B*27 typing was done by an in-house PCR-SSP technique in SpA patients to exclude B*27 positive patients and PCR-SSOP technique was used to type 100 B*27 negative SpA patients and 100 controls from the same ethnicity. Frequency of B*07 was significantly increased (B*07: % PF 54 versus 18; OR 5.348; 95% CI 2.808–10.186; value 1.14E − 07), whereas frequency of B*40 was significantly decreased (B*40: % PF 17 versus 32; OR 0.435; 95% CI 0.222–0.850; value 0.013) when compared with B*27 negative controls. Among 100 SpA patients, 47 were undifferentiated spondyloarthritis and 33 patients were reactive arthritis patients. 40% of the patients were suffering from polyarticular arthritis, 35% had pauciarticular arthritis with knee joint, hip joint, ankle joint, and SI joint involvement. We conclude that B*07 was significantly associated with B27 negative spondyloarthropathy from Western India and majority of B*27 negative patients were uSpA. Devaraj J. Parasannanavar, Anjali Rajadhyaksha, and Kanjaksha Ghosh Copyright © 2014 Devaraj J. Parasannanavar et al. All rights reserved. Exploring T Cell Reactivity to Gliadin in Young Children with Newly Diagnosed Celiac Disease Mon, 03 Mar 2014 16:46:37 +0000 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 - and -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 -gliadin than -gliadin peptides with a single deamidated -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. Edwin Liu, Kristen McDaniel, Stephanie Case, Liping Yu, Bernd Gerhartz, Nils Ostermann, Gabriela Fankhauser, Valerie Hungerford, Chao Zou, Marcel Luyten, Katherine J. Seidl, and Aaron W. Michels Copyright © 2014 Edwin Liu et al. All rights reserved. Chronic Exposure to Oral Pathogens and Autoimmune Reactivity in Acute Coronary Atherothrombosis Tue, 25 Feb 2014 12:24:32 +0000 Background. It has been hypothesized that various infective agents may activate immune reactions as part of the atherosclerotic process. We aimed to investigate the interrelationship between chronic exposure to oral pathogens and immune-inflammatory response in patients with acute coronary atherothrombosis. Patients and Methods. The study included 200 participants from Serbia: 100 patients with acute myocardial infarction (MI), and 100 age- and sex-matched controls. Antibodies to oral anaerobes and aerobes were determined as well as autoantibodies to endothelial cells, beta-2 glycoprotein I, platelet glycoprotein IIb/IIIa and anticardiolipin. Interleukin-6 (IL-6) and C-reactive protein (CRP) were measured. Results. The mean serum antibodies to oral anaerobes tended to be higher among subjects with MI (0.876 ± 0.303 versus 0.685 ± 0.172 OD, ). Similarly, antibody levels against oral aerobes in patients were significantly different from controls. Antibodies against endothelial cell, beta-2 glycoprotein I, platelet glycoprotein IIb/IIIa, anticardiolipin along with CRP and IL-6 were highly elevated in patients. The levels of antibodies to oral bacteria showed linear correlation with tissue antibodies, CRP and IL-6. Conclusion. Antibody response to chronic oral bacterial infections and host immune response against them may be responsible for the elevation of tissue antibodies and biomarkers of inflammation which are involved in acute coronary thrombosis development. Ivana Burazor and Aristo Vojdani Copyright © 2014 Ivana Burazor and Aristo Vojdani. All rights reserved. Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure Thu, 20 Feb 2014 10:52:33 +0000 Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences. Kathleen M. Gilbert, William Woodruff, and Sarah J. Blossom Copyright © 2014 Kathleen M. Gilbert et al. All rights reserved. Evaluation of SLE Susceptibility Genes in Malaysians Tue, 18 Feb 2014 09:45:27 +0000 Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (). The strongest signal was at HLA-DRA (; , ); the strongest non-HLA signal occurred at STAT4 (; , ). Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies. Julio E. Molineros, Kek Heng Chua, Celi Sun, Lay Hoong Lian, Prasenjeet Motghare, Xana Kim-Howard, and Swapan K. Nath Copyright © 2014 Julio E. Molineros et al. All rights reserved. A Potential Link between Environmental Triggers and Autoimmunity Wed, 12 Feb 2014 08:39:48 +0000 Autoimmune diseases have registered an alarming rise worldwide in recent years. Accumulated evidence indicates that the immune system's ability to distinguish self from nonself is negatively impacted by genetic factors and environmental triggers. Genetics is certainly a factor, but since it normally takes a very long time for the human genetic pattern to change enough to register on a worldwide scale, increasingly the attention of studies has been focused on the environmental factors of a rapidly changing and evolving civilization. New technology, new industries, new inventions, new chemicals and drugs, and new foods and diets are constantly and rapidly being introduced in this fast-paced ever-changing world. Toxicants, infections, epitope spreading, dysfunctions of immune homeostasis, and dietary components can all have an impact on the body's delicate immune recognition system. Although the precise etiology and pathogenesis of many autoimmune diseases are still unknown, it would appear from the collated studies that there are common mechanisms in the immunopathogenesis of multiple autoimmune reactivities. Of particular interest is the citrullination of host proteins and their conversion to autoantigens by the aforementioned environmental triggers. The identification of these specific triggers of autoimmune reactivity is essential then for the development of new therapies for autoimmune diseases. Aristo Vojdani Copyright © 2014 Aristo Vojdani. All rights reserved. A Metabolomic Perspective on Coeliac Disease Sun, 09 Feb 2014 09:25:53 +0000 Metabolomics is an “omic” science that is now emerging with the purpose of elaborating a comprehensive analysis of the metabolome, which is the complete set of metabolites (i.e., small molecules intermediates) in an organism, tissue, cell, or biofluid. In the past decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. A metabolomics investigation of coeliac disease (CD) revealed that a metabolic fingerprint for CD can be defined, which accounts for three different but complementary components: malabsorption, energy metabolism, and alterations in gut microflora and/or intestinal permeability. In this review, we will discuss the major advancements in metabolomics of CD, in particular with respect to the role of gut microbiome and energy metabolism. Antonio Calabrò, Ewa Gralka, Claudio Luchinat, Edoardo Saccenti, and Leonardo Tenori Copyright © 2014 Antonio Calabrò et al. All rights reserved. Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects Thu, 06 Feb 2014 13:29:34 +0000 Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharp’s syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia. Emanuele Cozzani, Massimo Drosera, Giulia Gasparini, and Aurora Parodi Copyright © 2014 Emanuele Cozzani et al. All rights reserved.