Autoimmune Diseases The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. Idiopathic Uveitis and Familial Mediterranean Fever: Is There Any Relationship? Thu, 30 Jan 2014 11:19:06 +0000 Introduction. Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by attacks of fever and polyserositis. FMF is often associated with other autoimmune diseases such as rheumatoid arthritis, polyarteritis nodosa (PAN), and Behcet. Uveitis is an inflammatory process caused by underlying infectious and inflammatory disorders. This study investigates the probable relationship between idiopathic uveitis and FMF. Methods. Patients with idiopathic uveitis were analyzed for the 12 most common MEFV mutations (P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H, E148Q) by a reverse hybridization assay (FMF StripAssay,Vienna lab,Vienna, Austria). Results. 12 patients with idiopathic uveitis were enrolled in this study. 10 of them were female. The youngest patient was a 7-year-old child and the oldest was 57. The most common complaints of patients were blurred vision and then eye redness. One patient was heterozygous for R761H. Genetic analysis of the 12 most common MEFV mutations in the patients with idiopathic uveitis didnot have any positive results. Conclusion. According to the analysis of the 12 most common MEFV gene mutations, FMF is not an underlying cause of idiopathic uveitis. On the other hand, uveitis merely could not be the first presentation of FMF. Farhad Salehzadeh, Ozra Yasrebi, Mahsa Hosseini Khotbesara, and Maryam Hosseini Khotbesara Copyright © 2014 Farhad Salehzadeh et al. All rights reserved. A Comparison of Anti-Nuclear Antibody Quantification Using Automated Enzyme Immunoassays and Immunofluorescence Assays Tue, 28 Jan 2014 07:49:17 +0000 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 (, 84%); however, 8% () yielded equivocal results (equivocal-negative and equivocal-positive) and 8% () 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. Renata Baronaite, Merete Engelhart, Troels Mørk Hansen, Gorm Thamsborg, Hanne Slott Jensen, Steen Stender, and Pal Bela Szecsi Copyright © 2014 Renata Baronaite et al. All rights reserved. Silent Burdens in Disease: Fatigue and Depression in SLE Tue, 28 Jan 2014 07:31:22 +0000 At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE. R. Fonseca, M. Bernardes, G. Terroso, M. de Sousa, and M. Figueiredo-Braga Copyright © 2014 R. Fonseca et al. All rights reserved. The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease Mon, 27 Jan 2014 13:39:15 +0000 Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance. Christopher B. Toomey, David M. Cauvi, and Kenneth M. Pollard Copyright © 2014 Christopher B. Toomey et al. All rights reserved. Prevalence of Thyroid Autoimmunity in Children with Celiac Disease Compared to Healthy 12-Year Olds Mon, 27 Jan 2014 13:23:10 +0000 Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screening-detected, were identified. Per case, 4 referents were matched. Blood samples were analyzed for autoantibodies against thyroid peroxidase (TPOAb). The cut-off value for TPO positivity was set to 100 U/mL. Results. Altogether, 335 celiac disease cases were found. In the entire celiac disease group, 7.2% (24/335) had elevated titers of TPOAb compared to 2.8% (48/1695) of the referents. Among the previously diagnosed celiac disease cases, 7.5% (7/93, OR 2.8, 95% CI 1.2–6.4) was TPOAb positive and among screening-detected cases, 7.0% (17/242, OR 2.6, 95% CI 1.5–4.6) was TPOAb positive. Conclusion. Children with celiac disease showed a higher prevalence of thyroid autoimmunity. We could not confirm the hypothesis that untreated celiac disease is associated with increased risk of developing thyroid autoimmunity. Early initiation of celiac disease treatment might not lower the risk for other autoimmune diseases. Maria van der Pals, Anneli Ivarsson, Fredrik Norström, Lotta Högberg, Johan Svensson, and Annelie Carlsson Copyright © 2014 Maria van der Pals et al. All rights reserved. Genes Associated with SLE Are Targets of Recent Positive Selection Thu, 23 Jan 2014 12:10:00 +0000 The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus (SLE) and the relative high frequency of SLE risk alleles in the population are not fully understood. Population genetic factors such as natural selection alter allele frequencies over generations and may help explain the persistence of such common risk variants in the population and the differential risk of SLE. In order to better understand the genetic basis of SLE that might be due to natural selection, a total of 74 genomic regions with compelling evidence for association with SLE were tested for evidence of recent positive selection in the HapMap and HGDP populations, using population differentiation, allele frequency, and haplotype-based tests. Consistent signs of positive selection across different studies and statistical methods were observed at several SLE-associated loci, including PTPN22, TNFSF4, TET3-DGUOK, TNIP1, UHRF1BP1, BLK, and ITGAM genes. This study is the first to evaluate and report that several SLE-associated regions show signs of positive natural selection. These results provide corroborating evidence in support of recent positive selection as one mechanism underlying the elevated population frequency of SLE risk loci and supports future research that integrates signals of natural selection to help identify functional SLE risk alleles. Paula S. Ramos, Stephanie R. Shaftman, Ralph C. Ward, and Carl D. Langefeld Copyright © 2014 Paula S. Ramos et al. All rights reserved. Advances in Neuroimmunology: From Bench to Bedside Sun, 19 Jan 2014 12:27:35 +0000 Cristoforo Comi, Umberto Dianzani, Filippo Martinelli Boneschi, and Daniel L. Menkes Copyright © 2014 Cristoforo Comi et al. All rights reserved. Rituximab for Remission Induction and Maintenance in Refractory Systemic Lupus Erythematosus Thu, 16 Jan 2014 15:14:40 +0000 Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with high morbidity if untreated. Sometimes, despite aggressive treatments, the disease remains active with cumulative organic damage. We conducted a retrospective and descriptive observational study of patients with SLE refractory to conventional treatment who were treated with rituximab (RTX) as remission induction therapy and maintenance. There was a significant reduction in the conventional immunosuppressive drug dose and the number of relapses of disease. RTX appeared to be effective and safe for the induction and maintenance of remission in patient with SLE refractory to conventional treatment. Fabio Bonilla-Abadía, Nicolás Coronel Restrepo, Gabriel J. Tobón, Andrés F. Echeverri, Evelyn Muñoz-Buitrón, Andres Mauricio Castro, Mercedes Andrade Bejarano, and Carlos A. Cañas Copyright © 2014 Fabio Bonilla-Abadía et al. All rights reserved. Evaluation of a Multiplex ELISA for Autoantibody Profiling in Patients with Autoimmune Connective Tissue Diseases Thu, 16 Jan 2014 12:08:13 +0000 The performance of immunoassays for the detection of autoantibodies is of critical importance in the diagnosis and assessment of patients with autoimmune connective tissue diseases (ACTD). Our objective was to compare the features of two multiplexed assays—INNO-LIA ANA and Gennova-PictArray ENA ELISA—for measurement of multiple autoantibodies and their utility as a clinical tool in ACTD diagnosis. The antigens included SS-A/Ro (60 and 52), SSB/La, Sm, Sm/RNP, CENP-B, Jo-1, and Scl-70. Stored sera from 85 ACTD patients and 80 controls consisting of patients with vasculitis, rheumatoid arthritis and infectious diseases, as well as healthy subjects were analyzed jointly with clinical and laboratory data. Agreement between the two methods varied between 58 and 99% (Cohen’s kappa: 0.21–0.71) mostly for SSA and SSB. The frequency of specific autoantibodies measured using the two methods was more variable for SSA, SSB, and RNP/Sm. There were a higher number of ambiguous results when using INNO-LIA. The optimized cut-off values of the Gennova-PictArray resulted in over 99% specificities in samples obtained from the control group. Sensitivity patterns were more accurate in Gennova-PictArray than in INNO-LIA, as suggested in previously reported studies. A third method could be applied to determine which of the two methods is more accurate. Alejandro Caro Pérez, Sarita Kumble, Krishnanand D. Kumble, M. Consuelo Alonso Cañizal, Luis M. Jiménez Jiménez, Lorena Alonso Díez, and Pilar Durán Parejo Copyright © 2014 Alejandro Caro Pérez et al. All rights reserved. Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: From Molecular Bases to Practical Considerations Tue, 14 Jan 2014 11:02:30 +0000 Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues. Paolo Ripellino, Thomas Fleetwood, Roberto Cantello, and Cristoforo Comi Copyright © 2014 Paolo Ripellino et al. All rights reserved. Pulmonary Arterial Hypertension in Patients with Primary Sjögren’s Syndrome Thu, 09 Jan 2014 12:28:53 +0000 Introduction. Primary Sjögren’s syndrome (pSS) is an autoimmune epithelitis. Pulmonary arterial hypertension (PAH) is an important and severe complication, which is encountered in many collagen tissue disorders. Early diagnostic strategies are required to define it at the asymptomatic stage. Doppler echocardiography is an important, noninvasive screening test for PAH diagnosis. Objective. The aim of this present study is to define the frequency of PAH in patients with pSS and to reveal correlations with laboratory and clinical findings. Material and Methods. A total of 47 patients, who were diagnosed with pSS according to American-European Study Group criteria were enrolled in the study. After all patients were evaluated clinically and by laboratory tests, Doppler echocardiography was performed in the cardiology outpatient clinic. Systolic pulmonary artery pressure (SPAP) >30 mm Hg values, which were measured at the resting state, were accepted as significant for PAH. Results. Forty-seven patients with pSS were included in the study. The mean age of patients was 48 years and the mean disease duration was 5.3 years. PAH was defined in 11 of the 47 patients (23.4%). The SPAP value was over 35 mm Hg in 5 out of 11 patients, whereas six patients had SPAP measuring 30–35 mm Hg. While pulmonary hypertension was related with earlier age and shorter duration of disease (), there was no statistically significant correlation between SPAP increase and clinical findings (). Conclusion. We have defined high PAH frequency in patients with pSS. Since there are different data in the literature, it is obvious that large scale, multicentre studies are required. Senol Kobak, Sezai Kalkan, Bahadır Kirilmaz, Mehmet Orman, and Ertuğurul Ercan Copyright © 2014 Senol Kobak et al. All rights reserved. An Update in Guillain-Barré Syndrome Mon, 06 Jan 2014 11:01:37 +0000 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. J. B. Winer Copyright © 2014 J. B. Winer. All rights reserved. Current Understanding on the Role of Standard and Immunoproteasomes in Inflammatory/Immunological Pathways of Multiple Sclerosis Thu, 02 Jan 2014 13:23:14 +0000 The ubiquitin-proteasome system is the major intracellular molecular machinery for protein degradation and maintenance of protein homeostasis in most human cells. As ubiquitin-proteasome system plays a critical role in the regulation of the immune system, it might also influence the development and progression of multiple sclerosis (MS). Both ex vivo analyses and animal models suggest that activity and composition of ubiquitin-proteasome system are altered in MS. Proteasome isoforms endowed of immunosubunits may affect the functionality of different cell types such as CD8+ and CD4+ T cells and B cells as well as neurons during MS development. Furthermore, the study of proteasome-related biomarkers, such as proteasome antibodies and circulating proteasomes, may represent a field of interest in MS. Proteasome inhibitors are already used as treatment for cancer and the recent development of inhibitors selective for immunoproteasome subunits may soon represent novel therapeutic approaches to the different forms of MS. In this review we 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. Elena Bellavista, Aurelia Santoro, Daniela Galimberti, Cristoforo Comi, Fabio Luciani, and Michele Mishto Copyright © 2014 Elena Bellavista et al. All rights reserved. Autoimmunity Diseases of the Skin Mon, 30 Dec 2013 11:33:28 +0000 Jozélio Freire Carvalho, Paulo Ricardo Criado, Valéria Aoki, and Yehuda Shoenfeld Copyright © 2013 Jozélio Freire Carvalho et al. All rights reserved. Severe Skin Forms of Psoriasis in Black Africans: Epidemiological, Clinical, and Histological Aspects Related to 56 Cases Sun, 29 Dec 2013 11:33:47 +0000 Bacground. Psoriasis is an erythematosquamous dermatosis of chronic development. In sub-Saharan Africa, few studies have been focused on complicated forms of psoriasis. Objective. The aim is to describe epidemiological, clinical, and histological features of severe skin forms of psoriasis in Cote d’Ivoire. Material and Methods. The study was both cross-sectional and descriptive, that focused on patient admitted to the dermatology unit for complicated psoriasis, from January 1st, 1986, to December 31th, 2007. Results. Fifty-six patients admitted to hospital for severe skin forms of psoriasis were recorded and included in our study over 7.503 patients hospitalized during the study period. They represented 0.75% of cases. The average age was 39.6 ± 3.3 years. There were 49 male (87.5%) and 7 female patients (12.5%) with a sex ratio of 7. At socioprofessional level, 48 patients (87.5%) were from category 1. Patients’ history was dominated by the psoriasis vulgaris. Physical and general signs were dominated by itching (58.9%). The three severe skin forms were observed with predominant erythrodermic psoriasis (60.7%). Fifteen patients (34.9%) were HIV positive. Conclusion. Severe skin forms of psoriasis are rare in our setting. But in the quarter of HIV-positive patients, they are dominated by the erythrodermic psoriasis. Komenan Kassi, Oussou Armel Mienwoley, Mohamed Kouyate, Sylvanus Koui, and Kouame A. Kouassi Copyright © 2013 Komenan Kassi et al. All rights reserved. Immunotherapy of Neuromyelitis Optica Wed, 25 Dec 2013 09:02:18 +0000 Neuromyelitis optica (NMO) is a chronic inflammatory disease of the central nervous system that affects the optic nerves and spinal cord resulting in visual impairment and myelopathy. There is a growing body of evidence that immunotherapeutic agents targeting T and B cell functions, as well as active elimination of proinflammatory molecules from the peripheral blood circulation, can attenuate disease progression. In this review, we discuss the immunotherapeutic options and the treatment strategies in NMO. We also analyze the pathogenic mechanisms of the disease in order to provide recommendations regarding treatments. Benjamin Bienia and Roumen Balabanov Copyright © 2013 Benjamin Bienia and Roumen Balabanov. All rights reserved.