Autoimmune Diseases The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Detection of Antibodies against Human and Plant Aquaporins in Patients with Multiple Sclerosis Sun, 26 Jul 2015 11:10:28 +0000 Multiple sclerosis (MS) is an autoimmune disease that affects the body’s central nervous system. Around 90% of MS sufferers are diagnosed with relapsing-remitting MS (RRMS). We used ELISA to measure IgG, IgA, and IgM antibodies against linear epitopes of human and plant aquaporins (AQP4) as well as neural antigens in RRMS patients and controls to determine whether patients suffering from RRMS have simultaneous elevations in antibodies against these peptides and antigens. In comparison to controls, significant elevations in isotype-specific antibodies against human and plant AQP4 and neural antigens such as MBP, MOG, and S100B were detected in RRMS patients, indicating a high correlation in antibody reaction between plant aquaporins and brain antigens. This correlation between the reactivities of RRMS patients with various tested antigens was the most significant for the IgM isotype. We conclude that a subclass of patients with RRMS reacts to both plant and human AQP4 peptides. This immune reaction against different plant aquaporins may help in the development of dietary modifications for patients with MS and other neuroimmune disorders. Aristo Vojdani, Partha Sarathi Mukherjee, Joshua Berookhim, and Datis Kharrazian Copyright © 2015 Aristo Vojdani et al. All rights reserved. Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats Sun, 26 Jul 2015 06:45:06 +0000 Objective. Achyranthes aspera Linn. (AA) is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR) fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction of Achyranthes aspera in adjuvant-induced arthritic rats. Methods. Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine and in vivo antioxidant parameters were measured on the last day of the study. Results. SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints. Conclusion. These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats. Pankaj S. Kothavade, Vipin D. Bulani, Dnyaneshwar M. Nagmoti, Padmini S. Deshpande, Nitin B. Gawali, and Archana R. Juvekar Copyright © 2015 Pankaj S. Kothavade et al. All rights reserved. Understanding and Managing Pregnancy in Patients with Lupus Sun, 12 Jul 2015 09:08:40 +0000 Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6–12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies. Guilherme Ramires de Jesus, Claudia Mendoza-Pinto, Nilson Ramires de Jesus, Flávia Cunha dos Santos, Evandro Mendes Klumb, Mario García Carrasco, and Roger Abramino Levy Copyright © 2015 Guilherme Ramires de Jesus et al. All rights reserved. Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study Sun, 12 Jul 2015 09:05:56 +0000 Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1) levels in patients with biopsy-proven lupus nephritis (LN) at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN—active or inactive—had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine) were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC) curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated. Sabah Alharazy, Norella C. T. Kong, Marlyn Mohd, Shamsul A. Shah, Arbaiyah Ba’in, and Abdul Halim Abdul Gafor Copyright © 2015 Sabah Alharazy et al. All rights reserved. Association between Secondary and Primary Sjögren’s Syndrome in a Large Collection of Lupus Families Sun, 12 Jul 2015 08:23:51 +0000 Objective. Systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) share clinical and immunogenetic features and may occur together. We undertook this study to determine the risk of primary SS among SLE-unaffected relatives of SLE patients and whether or not primary and secondary SS tended to occur in the same families. Methods. We collected clinical and serological data on 2694 SLE patients, 7390 SLE-unaffected relatives of the SLE patients, and 1470 matched controls. Results. Of the 2694 subjects with SLE, 548 had secondary SS, while 71 of their 7390 SLE-unaffected relatives had primary SS. None of the 1470 controls had SS as defined herein ( compared to SLE-unaffected relatives). Of the 71 SLE-unaffected relatives with primary SS, 18 (25.3%) had an SLE-affected family member with secondary SS, while only 530 of the 7319 (7.2%) SLE-unaffected relatives without SS did so (). Conclusion. Among families identified for the presence of SLE, primary and secondary SS tend to occur within the same families. These results highlight the commonalities between these two forms of SS, which in fact correspond to the same disease. Rachna Aggarwal, Juan-Manuel Anaya, Kristi A. Koelsch, Biji T. Kurien, and R. Hal Scofield Copyright © 2015 Rachna Aggarwal et al. All rights reserved. Predisposition to Cervical Atypia in Systemic Lupus Erythematosus: A Clinical and Cytopathological Study Thu, 09 Jul 2015 12:42:17 +0000 Introduction. Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course, and prognosis. The female genital tract may be a potential target organ in SLE since cervical inflammation may be associated with disease activity. An increase in cervical dysplasia, a precursor of cervical cancer, has been reported in females with SLE. Aim of the Work. This work aimed to study the prevalence of abnormal cervicovaginal smears in patients with systemic lupus erythematosus (SLE) and to correlate abnormal smear findings with exposure to infection with human papilloma virus (HPV) in SLE patients. Patients and Methods. Thirty-two patients with SLE, fulfilling the 1997 revised criteria for the classification of SLE, were included in this study. They were subjected to full history taking, clinical examination, laboratory investigations, and cervicovaginal smearing. Twenty healthy subjects not known to suffer from any rheumatological disease were used as controls, and they were subjected to cervicovaginal smearing. Results. Four out of 32 SLE patients showed abnormal Pap smears (12.5%) compared to none showing any cervical changes in the control group (0%). Among these 4 patients, 3 were having ASCU and one was having LSIL (HPV). Conclusion. Cervicovaginal smearing is an easy, economic, safe, repeatable, and noninvasive technique for screening and early detection of cervical neoplastic lesions in SLE. Hend Hilal Al-Sherbeni, Ahmed Mohamed Fahmy, and Nadine Sherif Copyright © 2015 Hend Hilal Al-Sherbeni et al. All rights reserved. Pathophysiological Relationship between Infections and Systemic Vasculitis Tue, 07 Jul 2015 11:50:55 +0000 The development of autoimmune disorders requires a combination of genetic, immunological, and environmental factors. Infectious agents, such as viruses and bacteria, can trigger autoimmunity through different mechanisms, and for systemic vasculitis in particular, microbial agents have been suggested to be involved in its pathogenesis. Although the exact mechanisms have not been fully elucidated, different theories have been postulated. This review considers the role of infections in the etiology of primary vasculitis, emphasizing their related immunological events. Carolina Muñoz-Grajales and Juan C. Pineda Copyright © 2015 Carolina Muñoz-Grajales and Juan C. Pineda. 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.