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Background There is no agreement on the prevalence of anti-phospholipid antibodies (aPLs) and the correlation with atherosclerosis and cardiovascular (CV) events in the general population. Methods We performed a cross-sectional study on 1712 randomly enrolled subjects from a Northern Italian city to investigate the presence of aPLs and the association with subclinical atherosclerosis (using the carotid artery intima media thickness measured as inter-adventitia common carotid artery diameters - ICCAD) and retrospectively collected CV factors and events (i.e. acute myocardial infarction, stroke, and peripheral obliterans arterial vasculopathy) using physician-assisted questionnaires. We tested serum IgG, IgM, and IgA anti-cardiolipin, anti-beta2glycoprotein I (aGPI), and anti-phosphatidylserine-prothrombin antibodies. Results Positive aPLs were found in 15.1% of the subjects, with no differences between sex but with higher rates in older subjects. Carotid subclinical atherosclerosis was more frequent in aPL positive subjects; more specifically, aGPI IgA were associated with higher ICCAD average (adjusted beta 0.51, 95% confidence interval (CI)0.17–0.84; p = 0.003). A positive history of CV events was also more frequent in aPL positive subjects (odds ratio (OR) 1.67, 95%CI 1.08–2.54; p = 0.012), particularly peripheral obliterans arterial vasculopathy ( OR 2.02 ; 95%CI 1.14–3.57; p = 0.015). Among subjects with a Framingham risk score >20, and/or diabetes, and/or body mass index >3 5 kg/m 2 , aPL positivity was associated to the highest risk of CV events (OR 2.52, 95%CI 1.24–5.11; p = 0.011). Conclusions APL prevalence in the general population is higher than previously reported. CV events and subclinical atherosclerosis are more frequent in the presence of aPL, particularly when a high CV risk coexists.

The present issue of the International Journal of Celiac Disease contains multiple aspects of celiac disease, spanning rare and new clinical presentations, associated conditions, reminds us on the lectin hypothesis of celiac disease, new epidemiological data on Africa, explore compliance with gluten elimination and describes the "waste bin diagnosis" of Sprue-like intestinal disease. Following is an overview of the issue content with a drop of a personal dip. Congratulations to the Editor and the Editorial Board of the International Journal of Celiac Disease (CD) for publishing volume 7, No 3 issue of the Journal.

Due to the recent interest in food additives that can act as triggering factors in autoimmune diseases including celiac disease (CD), the present letter to the editor expands on the microbial transglutaminase (mTG). It is heavily consumed by a plethora of food processing industries as "glue of proteins" thus improving product's stability, texture and shelf life. However, more and more information is accumulated lately, questioning its safety. Its cross-linked gliadin complexes are immunogenic in CD. The enzyme increases gliadin uptake, is transported in a trans-epithelial way and deposited below the enterocyte's line, has anti- phagocytic activity, enhances intestinal permeability and creates luminal resistant isopeptide bonds. No doubt that mTG is beneficial to food industries but a caveat to public health is highly recommended.

Most patients affected by celiac disease (CD) are asymptomatic or hyposymptomatic and undiagnosed, and are at risk of preventable complications. Therefore, early diagnosis is highly recommended. Multiple diagnostic antibodies are available; the most frequently used is IgA to tissue transglutaminase (IgA-tTg). It may yield false results and, alone, does not address IgA deficiency. Recently, a new generation of anti-neo-epitope tTg check (IgG + IgA) has become available. It is highly sensitive and specific, covers IgA-deficient patients with CD, reflects intestinal damage, and has predictive potential in the diagnosis of CD.

Objective Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, was undertaken to compare the sensitivity and specificity of anti-CD74 and HLA-B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA). Methods Patients ages 18-45 years with inflammatory back pain of ≤2 years' duration and a clinical suspicion of axSpA were recruited. HLA-B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty-nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed. Results One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti-CD74 and IgG anti-CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti-CD74 and IgG anti-CD74 was 95.3%. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74), and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti-CD74, 15.3% for IgG anti-CD74, and 28.8% for HLA-B27. A combination of IgA anti-CD74 and HLA-B27 results in a posttest probability of 80.2%. Conclusion IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation.

In intestinal diseases there are ophthalmological abnormalities. In celiac disease, for example, the eyes' pathologies are expressed by motoric, neurological, inflammatory, autoimmune, vision sharpness, dryness, redness, conjunctivitis and cataract tendency etc. It appears that intestinal luminal components and processes can irradiate to peripheral organs, including to the eyes, inducing functional abnormalities in this target organ. The present review describes the luminal and mucosal constituents and processes, the sensing mechanisms of those generated signals and the routes to deliver those messages to remote organs, eyes included. The gut-eye axis is very challenging and its exploration might bring future therapeutic strategies to treat ophthalmological disease.

Microbial transglutaminase (mTG) is a survival factor for microbes, but yeasts, fungi, and plants also produce transglutaminase. mTG is a cross-linker that is heavily consumed as a protein glue in multiple processed food industries. According to the manufacturers’ claims, microbial transglutaminase and its cross-linked products are safe, i.e., nonallergenic, nonimmunogenic, and nonpathogenic. The regulatory authorities declare it as “generally recognized as safe” for public users. However, scientific observations are accumulating concerning its undesirable effects on human health. Functionally, mTG imitates its family member, tissue transglutaminase, which is the autoantigen of celiac disease. Both these transglutaminases mediate cross-linked complexes, which are immunogenic in celiac patients. The enzyme enhances intestinal permeability, suppresses mechanical (mucus) and immunological (anti phagocytic) enteric protective barriers, stimulates luminal bacterial growth, and augments the uptake of gliadin peptide. mTG and gliadin molecules are cotranscytosed through the enterocytes and deposited subepithelially. Moreover, mucosal dendritic cell surface transglutaminase induces gliadin endocytosis, and the enzyme-treated wheat products are immunoreactive in CD patients. The present review summarizes and updates the potentially detrimental effects of mTG, aiming to stimulate scientific and regulatory debates on its safety, to protect the public from the enzyme’s unwanted effects.

Matrix metalloproteinase-3 or MMP3 also known as stromelysin-1 is an enzyme that is actively involved in joint destruction in rheumatoid arthritis (RA) patients. Screening the last three decades, it appears that serum levels of MMP3 reflect positively RA disease activity, joint and bone injury, and radiological erosion and predict disease outcome and drug responsiveness as summarized in several publications reporting outcomes on more than 8000 patients with RA. MMP-3 monitoring should be embedded in the routine assessment and accompany therapeutic modalities, in personalized medical RA management.

In gluten dependent conditions the gluten free diet is the cornerstone of therapy, decreasing disease activity, improving health and quality of life and treating or preventing the associated complications. Gluten withdrawal implies strict and lifelong elimination not only of wheat, barley, rye, and wheat-contaminated oats, but also of numerous non-nutritional products where components of wheat are often added. Due to multiple reasons the diet is difficult to follow and the long-term adherence is decreased with time. The present review summarizes the dark side of gluten restriction where nutritional deficiencies, toxicity, morbidity, mortality, and mental health problems are reported. The aim being to increase awareness, avoid, detect and treat the side effects and to promote a healthier nutrition, for the patient's benefits.

Genetic risk factors for autoimmune diseases are constantly discovered, however, environmental factors are laggingbehind and the precipitating events leading to development of autoimmune diseases remain enigmatic. Gluten is a well-established inducing nutrient in celiac disease and gluten withdrawal is the only current effective therapy. More and more studies have shown that non-celiac autoimmune diseases can partially respond to gluten free diet. The present editorial reviews those conditions and suggest multiple potential mechanisms that might operate in clinical amelioration of non-celiac autoimmune diseases.

Celiac disease is a multi-organ disorder which is highly variable in its clinical expression, presenting multiple enteric and extraintestinal manifestations. However, most of treating physicians and dieticians regard celiac disease as a chronic, gradually evolving, asymptomatic or hypo-symptomatic entity. The present mini-review aims to screen the literature for acute presentations of celiac disease and to increase the awareness of the medical communities, for such a possibility. It appears that the disease can present acutely in multiple symptomatic, phenotypic and laboratory pictures. The acute presentation involves mainly the gastrointestinal tract and adjacentorgans like liver and gallbladder, however, extraintestinal and remote organs presentations can occur.

OBJECTIVE The aim of this study is to analyse the influence of LILRA3 and the genetic leukocyte immunoglobulin-like receptor 3 (LILRA3) deletion on transmission and clinical course of HIV infection. DESIGN Case and control study. METHODS LILRA3 genotypes were determined by PCR. HIV patients were categorized into short-term progressors, normal progressors and long-term nonprogressors according to the clinical course. Functional studies were performed using real-time PCR, intracellular flow cytometry and ELISA. RESULTS The prevalence of the homozygous LILRA3 deletion was higher in HIV-positive individuals (n = 439) than in controls (n = 651) (P = 0.02). The disease progression was faster in homozygously deleted patients with more short-term progressors than in heterozygous (P = 0.03) and homozygously positive (P = 0.002) individuals. These results have been confirmed in a seroconverter cohort (n = 288). The frequency of the homozygous deletion in the confirmation cohort was higher than in controls (P = 0.04). Combining both cohorts, the proportion of homozygously LILRA3-deleted individuals was 6.2% in HIV-infected patients (n = 727) vs. 3.2% in controls (P = 0.01). Functional analysis revealed an upregulation of the LILRA3 gene in real-time PCR in treated patients when compared with untreated patients (P = 0.007) and controls (P = 0.02) resulting in a higher LILRA3 expression in CD4 (P = 0.008) and CD14 (P = 0.02) cells of untreated patients in intracellular flow cytometry. LILRA 3 concentrations in the sera were similar between the groups, in untreated patients a correlation between viral load and LILRA3 concentration was found. CONCLUSION The homozygous LILRA3 deletion is associated with a higher susceptibility for HIV disease and with a faster disease progression.

Microbial transglutaminase (mTg) is capable of cross-linking numerous molecules. It is a family member of human tissue transglutaminase (tTg), and is involved in CD. Despite declarations of the safety of mTg for industrial use, direct evidence for immunogenicity of the enzyme is lacking. The serological activity of mTg, tTg, gliadin complexed mTg (mTg neo-epitope) and gliadin complexed tTg (tTg neo-epitope) were studied in 95 pediatric celiac patients (CD), 99 normal children (NC), 79 normal adults (NA) and 45 children with nonspecific abdominal pain (AP). Sera were tested by ELISAs, detecting IgA, IgG or both IgA and IgG (check): AESKULISA® tTg (tTg), AESKULISA® tTg New Generation (tTg neo-epitope (tTg-neo)), microbial transglutaminase (mTg) and mTg neo-epitope (mTg-neo). Marsh criteria were used for the degree of intestinal injury. Parallel, mTg and tTg neo-epitopes were purified by asymmetric field flow fractionation, confirmed by multi-light-scattering and SDS-PAGE, and analyzed in adult CD and control groups by competition ELISAs. No sequence homology but active site similarity were detected on alignment of the 2 Tgs. Comparing pediatric CD patients with the 2 normal groups: mTg-neo IgA, IgG and IgA + IgG antibody activities exceed the comparable mTg ones (p tTg-neo IgA ≥ mTg-neo IgG > tTg-neo IgG > mTg-neo check > mTg-neo IgA. Taken together, tTg-neo check, tTg-neo IgA and mTg-neo IgG correlated best with intestinal pathology (r2 = 0.6454, r2 = 0.6165, r2 = 0.5633; p mTg is immunogenic in children with CD and, by complexing to gliadin, its immunogenicity is enhanced. Anti-mTg-neo-epitope IgG antibodies correlate with intestinal damage to a comparable degree as anti-tTg-neo IgA. mTg and tTg display a comparable immunopotent epitope. mTg-neo IgG is a new marker for CD. Further studies are needed to explore the pathogenic potential of anti-mTg antibodies in CD.

Wheat is the most important source of carbohydrate in the Western world with a constant increase in sales also in Eastern societies. Since gluten comprises 80% of the contemporary wheat proteins an...

To study the association between the presence of antibodies against CD74 and structural damage in the sacroiliac joints and spine in patients with axial spondyloarthritis (axSpA).Antibodies against CD74 were measured in the sera of patients with axSpA from 2 cohorts: 1. An observational cohort from Damp in Northern Germany and 2. from a clinical trial (ENRADAS), in which the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) had been evaluated by two readers blinded to the time point at baseline and two years later. The presence of antibodies against CD74 was correlated with the presence and grade of radiographic sacroiliitis in the observational cohort, and with baseline mSASSS in the ENRADAS cohort.The sensitivity of IgA anti-CD74 antibodies for axSpA was 50% in the Damp cohort and 42% in ENRADAS. The presence of IgA antibodies against CD74 was associated with a higher grade of sacroiliitis (observational cohort) and a higher baseline mSASSS in the ENRADAS cohort.IgA antibodies against CD74 are not only markers of AS, but are associated with structural damage development in the sacroiliac joints and in the spine.

Most patients affected by celiac disease (CD) are asymptomatic or hyposymptomatic and undiagnosed, and are at risk of preventable complications. Therefore, early diagnosis is highly recommended. Multiple diagnostic antibodies are available; the most frequently used is IgA to tissue transglutaminase (IgA-tTg). It may yield false results and, alone, does not address IgA deficiency. Recently, a new generation of anti-neo-epitope tTg check (IgG + IgA) has become available. It is highly sensitive and specific, covers IgA-deficient patients with CD, reflects intestinal damage, and has predictive potential in the diagnosis of CD.

Spondyloarthritis (SpA) is a chronic inflammatory disease of unknown aetiology. Previously, we identified autoantibodies against CD74 in sera of SpA patients. The aim of this study was to evaluate CD74 as a T cell antigen in SpA.Recombinant CD74 protein and a panel of selected peptides representing its amino acid residues were examined for their capability to stimulate peripheral blood mononuclear cells from patients with SpA. In particular, cytokine production by CD4+ T cells was evaluated with flow cytometric detection of intracellular TNF-α, IFNγ, TGFβ and IL-17A. Patients' sera were tested for antibodies against CD74 using ELISA. Samples from patients with rheumatoid arthritis and healthy blood donors were similarly tested as controls.Significantly more CD4+ T cells from SpA patients produced TNF-α, IFNγ and IL-17A in response to recombinant CD74 than patients with rheumatoid arthritis or healthy blood donors. Among evaluated epitopes, the most promiscuous one lies within the peptide of the amino acid residues 142-185, which appeared more immunogenic. Further, the proportion of cytokine producing CD4+ T cells was significantly higher among SpA patients with autoantibodies against CD74.CD74 is a T cell antigen in SpA, eliciting Th1 and Th17 responses, which may be relevant in disease pathogenesis. Recognition of the highly immunogenic amino acid residues of CD74 may contribute to our understanding of autoimmune responses of T helper cells in SpA.

Gluten is a major constituent in modern human food and its industrial applications are expanding constantly. Its increasing consumption, evolutionary increased content in wheat, and enhanced toxicity and immunogenicity make it a prime candidate as a modern environmental factor that might impact autoimmunogenesis. Its capacity to change the balance between microbiome and dysbiome, being a good substrate for PTMP, to disrupt tight junction functional integrity resulting in a leaky gut and its multiple side effects represent mode of actions that might drive autoimmune diseases' (ADs) initiation, maintenance, and progression. Its beneficial effects, when withdrawn in multiple ADs, further reinforce its place in impacting autoimmunity. Further exploration on its potential detrimental effects on human health may be beneficial for the autoimmune affected populations.

Microbial transglutaminase (mTG) is a survival factor for bacteria that is heavily used as a protein glue in the processed food industries. Despite the manufacturers’ claims for it safe usage, scientific observations are accumulating for its unwanted effects on human health. The enzyme can cross link proteins, imitating its family member, tissue transglutaminase, the autoantigen of celiac disease. Its gliadin cross-linked complexes are immunogenic in celiac disease. In the intestinal lumen, mTG exerts anti protease activity and forms resistant isopeptide bonds, it is anti-phagocytic, thus suppressing luminal protective pathways. It increases intestinal permeability, is trans-epithelialy transported and faces the enteric mucosal immune cells. Finally, mTG-containing products can react as emulsifiers and mucolytic agents thus compromising barriers’ integrities. The present review summarizes and updates on the potential detrimental effects of mTG, aiming to protect the public from the enzyme’s unwanted effects.

Background: Adolescence is a vulnerable period for the development of nutritional anemia. Aim: To evaluate the determinants of iron deficiency, anemia, and associated factors among adolescents who performed routine blood tests in a large district in Israel during 2014. Methods: A community-based cross-sectional observational study was conducted among adolescents aged 11-18 years, belonging to Haifa and west Galilee district of ‘Clalit’ Health Services, who routinely performed blood tests during 2014. The blood tests were investigated for iron deficiency (ferritin

Objective Anti-ribosomal-phosphoprotein antibodies (anti-Ribos.P Abs) are detected in 10–45% of NPSLE patients. Intracerebroventricular administration of anti-ribosomal-P Abs induces depression-like behaviour in mice. We aimed to discern the mechanism by which anti-Ribos.P Abs induce behavioural changes in mice. Methods Anti-Ribos.P Abs were exposed to human and rat neuronal cell cultures, as well as to human umbilical vein endothelial cell cultures for a control. The cellular localization of anti-Ribo.P Abs was found by an immunofluorescent technique using a confocal microscope. Identification of the target molecules was undertaken using a cDNA library. Immunohistochemistry and an inhibition assay were carried out to confirm the identity of the target molecules. Neuronal cell proliferation was measured by bromodeoxyuridine, and Akt and Erk expression by immunoblot. Results Human anti-Ribos.P Abs penetrated into human neuronal cells and rat hippocampal cell cultures in vitro, but not to endothelial cells as examined. Screening a high-content human cDNA-library with anti-Ribos.P Abs identified neuronal growth–associated protein (GAP43) as a target for anti-Ribos.P Abs. Ex vivo anti-Ribos.P Abs bind to mouse brain sections of hippocampus, dentate and amygdala. Anti-Ribos.P Abs brain-binding was prevented by GAP43 protein. Interestingly, GAP43 inhibited in a dose-dependent manner the anti-Ribos.P Abs binding to recombinant-ribosomal-P0, indicating mimicry between the ribosomal-P0 protein and GAP43. Furthermore, anti-Ribos.P Abs reduced neuronal cell proliferation activity in vitro (P < 0.001), whereas GAP43 decreased this inhibitory activity by a factor of 7.6. The last was related to Akt and Erk dephosphorylation. Conclusion Anti-Ribos.P Abs penetrate neuronal cells in vitro by targeting GAP43. Anti -Ribos.P Abs inhibit neuronal-cell proliferation via inhibition of Akt and Erk. Our data contribute to deciphering the mechanism for anti-Ribos.P Abs’ pathogenic activity in NPSLE.

Detection of IgA-transglutaminase2 (TG2) autoantibodies has become the test of choice for the diagnosis and monitoring of celiac disease (CD), and is recommended as the serological ‘gold standard’ by most of the CD societies. Despite its wide acceptance and reasonable performance, several aspects are problematic and disputed. The normal range levels between positivity and negativity are modified, manufacturers’ cut-off levels are extremely variable, far from matching in house determinations, insufficient standardization, inadequate reference protocols and no reliable quality assessment of the ELISA antibody (AB) kits for CD diagnosis and follow-up of dietary adherence. Numerous limitations exist in its detection, diagnosis, and follow-up capacities, resulting in frequent clinical circumstances when professionals encounter false positive and negative situations. The present review updates and discusses these facets and aims to extend our knowledge and help CD associated professionals to use the IgA-TG2 antibodies appropriately. We hope that the content of the review will stimulate the scientific community to explore and better delineate the role and functions of the AB and the industrial manufacturers to improve clinical performance of their diagnostic tests.

Metabolic bone disease is a frequent extra-intestinal co-morbidity in newly diagnosed, mostly adult patients who have 70% low bone mineral density. Musculoskeletal signs and symptoms, osteopenia, osteoporosis and fractures are the most frequent manifestations. The etiology is multifactorial, however, micronutrient malabsorption, mainly of calcium and vitamin D, secondary hyperparathyroidism and inflammation are the main driving forces. The diagnosis is based on signs and symptoms, biochemical and endocrinologic laboratory evaluation and imaging by dual x-ray absorptiometry. Treatment of low bone mineral density in CD comprises: a gluten free diet, coverage of nutritional deficiencies (including calcium and vitamin D), changes in life style and if necessary, pharmacologic and hormonal replacement therapy. The cost effectiveness of those therapy methods were barely assessed. Understanding the pathophysiology of bone loss in celiac disease might bring new therapeutical strategies for the patient’s benefit.

The surge in incidence of celiac disease (CD) is due more to environmental than to genetic changes. It is paralleled by a food industry that is continuously introducing additives to processed products. Microbial transglutaminase (mTG) is an enzyme that deamidates/transamidates proteins, enabling cross-linkage of molecules and revolutionizing the properties of many food products. It belongs to the family of transaminases and tissue transglutaminase (tTG) has been identified as the autoantigen in CD. Both enzymes de/transamidate gluten, the nutritional environmental factor that induces CD. Although several studies have shown that mTG transamidation of wheat flour/gluten can detoxify gluten peptide in vitro, by inhibiting the response to intestinal gliadin, inducing T cells and reducing INFγ production without influencing their main technological properties, a word of caution is advised. The oral challenge of adult CD patients with mTG transamidated flour was found to be only partially effective, not fulfilling expectations, and there have been multiple recent observations that indicate that mTG transamidated flour/gluten could be dangerous to gluten sensitive populations: mTG cross-linking of gluten may be hazardous in CD since the enzyme can deamidate gluten, thus mimicking endogenous tTG, it can link an extensive repertoire of proteins and other macromolecules with immunogenic potential, mTG treated gluten peptides are immunogenic to celiac patients, inducing specific IgA antibodiesand are recognized by gluten-specific humanT cells. Their effect on CD intestinal permeability has not yet been studied. To better understand the actual processes and events, associated with the suggested mTG therapy, long-term ex vivo and in vitro studies are needed. Until then, it is best to respect the data but suspect the safety of the gluten sensitive populations.

Epidemiological data provide evidence of a steady rise in autoimmune disease throughout Westernized societies over the last decades. Multiple publications exist, describing past or actual incidences/prevalence of individual autoimmune diseases, however, long term studies on selected populations are scarce. Aims: to calculate the % increases per year of autoimmune diseases frequencies worldwide, analyze the differential increases per country and disease, and identify geoepidemiological trends. Methods: A systematic review was performed to identify incidence and prevalence of autoimmune diseases. 30 Studies from the last 30 years were identified using Medline, Google, and Cochrane Library databases. Only long-term regional or national follow-ups are reported. Results: The means ± s.d. of the net % increased /year incidence and prevalence of autoimmune diseases worldwide were 19.1±43.1 and 12.5±7.9, respectively. Rheumatic, endocrinological, gastrointestinal and neurological autoimmune diseases revealed the following annual % increases per year: 7.1, 6.3, 6.2, and 3.7, respectively. In all of these, differences between old vs new frequencies were highly significant (p< 0.0001). Comparing various autoimmune diseases, celiac disease increased the most and the highest increase in incidence, comparing old to new surveys is allocated to myasthenia gravis. Despite considerable variations between the countries, celiac, type 1 diabetes and myasthenia gravis frequencies increased the most in , and , respectively. Frequencies of the autoimmune diseases increased significantly in the West and North when compared to East and South, respectively. Conclusions: Despite multiple reports on autoimmune diseases frequencies, long-term longitudinal follow-ups are scarce. Incidences and prevalences have increased significantly over the last 30 years. Rheumatic, endocrinological and gastrointestinal autoimmune diseases in , , and increased the most. These observations point to a stronger influence of environmental factors as opposed to genetic factors on autoimmune disease development.

Background AESKUSLIDES ANCA is an indirect immunofluorescence assay used to detect anti-neutrophil cytoplasmic autoantibodies (ANCA) in human serum. This in vitro diagnostic assay is used as an aid for the diagnosis of ANCA-associated vasculitis (AAV) in conjunction with other clinical and laboratory findings. Methods A method comparison of ethanol and formalin fixed granulocytes was carried out between AESKUSLIDES ANCA (AESKU. Diagnostics) and the NOVA Lite ANCA of INOVA. 507 clinical serum samples (comprising 135 serum samples from patients with AAV and 375 samples from patients with other diseases) were analysed by standard IFA protocols. Results were obtained by manual processing and reading. Results In this cohort, AESKUSLIDES ANCA Ethanol slides show higher sensitivities (48.5% vs. 36.4%) and specificities (69.3% vs. 55.2%) compared to INOVA. AESKUSLIDES ANCA Formalin slides show higher sensitivities (50.0% vs. 37.9%) and similar specificities (90.7% vs 91.5%) compared to INOVA. Conclusions AESKUSLIDES ANCA Ethanol showed higher diagnostic sensitivity (48.5%) and specificity (69.3%) compared to the predicate assay NOVA Lite provided by INOVA (36.4%, 55.2%). This is due to the fact, that AESKU assay detects more positives in the AAV cohort, and less positives in the other disease groups. AESKUSLIDES ANCA Formalin showed a diagnostic sensitivity (50.0%) compared to the predicate assay NOVA Lite provided by INOVA (37.9%). However, the diagnostic sensitivity was comparable between the two (90.7% vs 91.5%). Disclosure of Interest None declared

Background The incidence of infectious diseases in the RA ADAPTHERA study by ELISA antibody screening and the differences in infectious distribution in active or low active disease patients was explored. Methods Sera from 88 naive RA patients out of the ADAPTHERA study cohort, disease duration Results 82% RA patients were found to be positive for HSV1 +2 IgG (2% IgM positive), 8% for Adenovirus (IgA), 77% (IgG), and 1% (IgM). 99% for EBV-IgG (no IgM positive). 53% (IgG), and 26% (IgM) for CMV. 38% for HP-IgG and 15% for IgA and 79% for P-B19-IgG (3% IgM). 6% for Borrelia-IgM and 14% for IgG. A slightly increase was found for EBV sera positivity (99% IgG), compared to the normal population. Conclusions Limited evidence exists regarding the impact of the disease activity on the susceptibility for infections, possibly due to the close association of RA disease activity and therapy dependent dosage of immunosuppressive treatment. Still, some infections may present memory contact, presenting an epiphenomenon. On the contrary, they might play an active role in RA pathophysiology. Disclosure of Interest None declared

In light of the coincident surge in overall gluten intake and the incidence of autoimmune diseases, the possible biological adverse effects of gluten were explored. PubMed, MEDLINE, and the Cochrane Library databases were screened for reports published between 1964 and 2016 regarding the adverse effects of gluten as well as the effects of a gluten-free diet on autoimmune diseases. In vitro and in vivo studies describing gluten intake in animal models or cell lines and gluten-free diets in human autoimmune diseases were reviewed. Multiple detrimental aspects of gluten affect human health, including gluten-dependent digestive and extradigestive manifestations mediated by potentially immunological or toxic reactions that induce gastrointestinal inadequacy. Gluten affects the microbiome and increases intestinal permeability. It boosts oxidative stress and affects epigenetic behavior. It is also immunogenic, cytotoxic, and proinflammatory. Gluten intake increases apoptosis and decreases cell viability and differentiation. In certain nonceliac autoimmune diseases, gluten-free diets may help curtail the adverse effects of gluten. Additional in vivo studies are needed to unravel the puzzle of gluten effects in humans and to explore the potential beneficial effects of gluten-free diets in autoimmune diseases.