Individual Autoimmune Diseases Research Articles

ABO and Rh blood group distribution in ANA positive patients

Aims: Antinuclear antibody (ANA) positivity is a common finding in various autoimmune diseases, particularly those of rheumatologic origin. While ANA positivity alone may not be diagnostic, it serves as a valuable marker when supported by clinical findings, aiding in the diagnosis and prediction of autoimmune diseases. The relationship between blood group systems and various diseases has been an area of interest in medical research. In this study, we aimed to investigate the potential association between ABO blood group and ANA positivity, specifically examining whether the ABO blood group status poses a risk for autoimmune diseases in individuals with rheumatologic conditions. Methods: In this retrospective study, we analyzed the blood group data of 536 patients who tested positive for ANA and were receiving treatment for rheumatologic diseases. The blood group status of these individuals was determined using standard serologic techniques. The distribution of ABO and Rh factor blood groups among ANA-positive patients was compared with the blood group distribution in the general population. Statistical analysis was performed to assess any significant differences. Results: The analysis revealed that the distribution of ABO and Rh factor blood groups among ANA-positive individuals did not show a statistically significant difference compared to the general population. Specifically, there was no significant deviation in the prevalence of ABO blood groups (A, B, AB, O) or Rh factor (positive or negative) among ANA-positive patients compared to expected frequencies based on population data. Conclusion: Based on our findings, there appears to be no significant association between ABO blood group status and ANA positivity in patients with rheumatologic diseases. The distribution of ABO and Rh blood groups among ANA-positive individuals closely resembled that of the general population. Therefore, our study suggests that current blood group status may not serve as a predictive factor for autoimmune diseases in individuals who test positive for ANA. Further research is warranted to explore other potential factors contributing to autoimmune disease susceptibility.

Graves’ disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study

BackgroundEpidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD). ObjectiveThe objective of this study is to establish a causal association between GD and autoimmune diseases. MethodsWe employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations. ResultsBidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases. ConclusionThis study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease

Rotavirus infection is a common cause of gastroenteritis in children that can trigger autoimmune processes, but the nature of this interaction remains poorly understood. To estimate the association of rotavirus infection with the risk of subsequent autoimmune disease. This population-matched cohort study used data from children and adolescents (aged younger than 18 years) in South Korea (national registers from January 1, 2002, to December 31, 2017). The cohort consisted of 86 157 patients in the exposure group who had experienced rotavirus-associated hospitalization and the same number of matched patients in the unexposed group. Data analyses were from May 1, 2020, through October 20, 2022. Hospitalization for rotavirus infection. The main outcome was childhood autoimmune diseases during the study defined by diagnoses according to the National Health Insurance Database. Hazard ratios (HRs) with 95% CIs for autoimmune diseases were estimated using a Cox model, with multiple confounding factors controlled. This cohort study consisted of 1 914 461 individuals born in South Korea from 2002 to 2005 who were potentially eligible. After exclusions, there were 86 517 individuals in the exposed group and 86 517 in the unexposed group after 1:1 incidence density sampling. The study included 49 072 (57.0%) male patients. The median (IQR) age at diagnosis of rotavirus-associated hospitalization was 1.5 (0.9-2.7) years, and the HR for autoimmune disease in the exposed group was 1.24 (95% CI, 1.19-1.28) for a mean (SD) follow-up time of 12.1 (3.2) years. The use of more stringent definitions for exposure and outcomes in a multivariable stratified analysis also indicated that rotavirus-associated hospitalization was associated with an increased risk of subsequent autoimmune disease (HR, 1.22 [95% CI, 1.16-1.28]). Sensitivity analysis showed that individuals with rotavirus-associated hospitalization was related to multiple autoimmune syndromes (2 or more: HR, 1. 51 [95% CI, 1. 31-1. 73]; 3 or more: HR, 1. 79 [95% CI, 1.18-2.72]) and that the number of rotavirus-associated hospitalization were associated with higher risks for autoimmune disease in a dose-dependent manner (single hospitalization event: HR, 1.20 [95% CI, 1.16-1.24]; multiple events HR, 1.60 [95% CI, 1.49-1.72]). Our results indicate that rotavirus-associated hospitalization is significantly associated with subsequent autoimmune disease during childhood. Clinicians should be aware of the heightened susceptibility to autoimmune disease in individuals with prior rotavirus-associated hospitalization.

Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis

ObjectiveThe VITAL trial of vitamin D supplementation suggested a possible protective effect for autoimmune diseases but uncertainties remain. We investigated potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization. MethodsWe used data from 332,984 participants of the UK Biobank of whom 23,089 had at least one autoimmune disease defined using ICD code and/or self-report. Diseases were further considered in mechanistic subgroups driven by “autoimmunity” (n = 12,774) or “autoinflammation” (n = 11,164), then individually. We selected variants within gene regions implicated in vitamin D biology to generate a weighted genetic score. We performed population-wide analysis using the ratio method, then examined non-linear effects across five quantiles based on 25-hydroxycholecalciferol levels. ResultsGenetically-predicted vitamin D was associated with lower risk of diseases in the autoinflammation group (OR 0.95 per 10 ng/ml increase in 25-hydroxycholecalciferol; 95%CI 0.91–0.99; p = 0.03) but not the autoimmunity group (OR 0.99; 95%CI 0.95–1.03; p = 0.64) or combined. When considering individual diseases, genetically-predicted vitamin D was associated with lower risk of psoriasis (OR 0.91; 95%CI 0.85–0.97; p = 0.005), the most common disease in the autoinflammation group, and suggestively with systemic lupus erythematosus (OR 0.84; 95%CI 0.69–1.02; p = 0.08); results were replicated using data from independent studies. We found no evidence for a plausible non-linear relationship between vitamin D and any outcome. ConclusionsWe found genetic evidence to support a causal link between 25-hydroxycholecalciferol concentrations and psoriasis and systemic lupus erythematosus. These results have implications for potential disease prevention strategies, and the interpretation and design of vitamin D supplementation trials.

Autoimmune disease and risk of postpartum venous thromboembolism

BackgroundThe risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. ObjectivesThe objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. MethodsUsing the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. ResultsIndividuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn’s disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. ConclusionAutoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn’s disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events.

Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case–control study

BackgroundAntibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general.MethodsFrom a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers.ResultsTotal number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08–2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs.ConclusionsUse of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA.ImpactIncreasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases.Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not.The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.

Increased Prevalence of Autoimmune Disease in Individuals with Down Syndrome and Moyamoya Disease (P9-10.001)

Increased Prevalence of Autoimmune Disease in Individuals with Down Syndrome and Moyamoya Disease (P9-10.001)

Literatur Review: Mata Kering Akibat Obat-Obatan

Dry eye disease is a disease that is often encountered and can occur due to several factors. This disease is more common in women than men. The risk factors that can cause dry eyes are divided based on individual characteristics, environment, chronic disease, autoimmune disease, medications and history of injury. The writing of this article was obtained from various sources in the form of scientific journals and guidelines for related institutions. Source searches were carried out on various online portals such as Medscape, NCBI, Google Scholar and other health websites with the keyword “Dry Eye Disease”, “Dry Eye Syndrome”, “Medications Causes Dry Eyes” Dry eye disease is a disease that is often encountered and occurs because it is multifactorial and can affect the quality of life and interfere with vision, especially when carrying out daily activities. One of the factors that cause dry eyes, namely the use of drugs, both topical drugs and systemic drugs. Concurrent use of five or more medications can increase the occurrence of dry eye. Management of dry eyes can be given artificial tears and stop using medications that trigger dry eyes or replace the drug with another drug. Dry eye disease can be caused by the use of drugs, both topical and systemic drugs. Treatment that can be done, namely by giving artificial tears and avoiding systemic or topical ophthalmic drugs that cause dry eyes.

Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data

Does preexisting or treatment-emergent autoimmunity increase the risk of subsequent autoimmune disease in individuals with relapsing-remitting multiple sclerosis (MS) after alemtuzumab? In the extended phase 2/3 trials, 34/96 (35.4%) patients with and 395/1120 (35.3%) without preexisting autoimmunity developed non-MS autoimmunity. Thyroid autoimmunity after alemtuzumab courses 1 or 2 did not increase subsequent non-thyroid autoimmune adverse events. Therefore, autoimmune disease before or after alemtuzumab treatment does not predict autoimmunity after further courses, so should not preclude adequate alemtuzumab dosing to control MS. Finally, post-marketing safety data contribute toward a full record of the alemtuzumab benefit/risk profile for the MS field.

Autoimmune Diseases, Infections, Use of Antibiotics and the Risk of Acute Myeloid Leukemia: A National Population-Based Case-Control Study

Background.Studies have suggested that chronic autoimmune diseases and infections increase the risk of myeloid malignancies. However, due to the strong association between exposure to cytotoxic agents and subsequent acute myeloid leukemia (AML) and a lack of clinical data in previous studies, it remains unclear whether the reported risk is caused by e.g. cytotoxic and immune modulating agents given to treat a variety of autoimmune diseases.MethodsTo investigate if acute and chronic inflammation per se increase the risk of AML or whether this association are explained by preceding cytotoxic therapy or hematological diseases, we conducted a nationwide case-control study using the Danish National Acute Leukemia Registry. We identified 3165 AML patients diagnosed 2000-2013 Patients were matched to population controls on sex and age through the Danish National Registry of Patients. To avoid recall bias, we retrieved individual-level information on inflammation measured as autoimmune disease, infections, and use of antibiotics through the Danish National Registry of Patients and the Danish National Health Service Prescription Database.We used conditional logistic regression analysis to compute odds ratios for AML. To avoid reverse causation, we ignored exposures ≤3 years before AML diagnosis/index date. Results were stratified by AML type (de novo AML, secondary AML or therapy-related AML), sex, and age. Results were given with 95% confidence intervals (CI).ResultsThe median age was 68.8 years (range 15-99) and 55% of the cases were men. Among cases, 74.1% had de novo AML, 19.1% had sAML, and 6.8% had tAML. Only 3.5% had APL.Overall, 239 (7.6%) of patients and 1847 (5.8%) of controls had an autoimmune disease diagnosis more than 3 years before their AML diagnosis or the index date. Having an autoimmune disease was associated with an overall increased risk of AML (OR 1.3 (CI=1.2-1.5)). However, the risk was only increased for sAML and tAML (OR 2.1 (CI=1.7-2.6)), and not for de novo AML (OR 1.1 (CI=0.9-1.3)).The association between infections and AML overall and by AML type is shown in Figure 1.Any hospitalization-requiring infection was associated with a higher risk of AML (OR 1.2 (CI=1.1-1.4)). Stratified by type of AML, this association was explained by a high risk of sAML/tAML (OR 1.8 (CI=1.5-2.2)) and not by de novo AML (OR 1.1 (CI=0.9-1.2)).To capture community-acquired infections, we used antibiotic prescriptions. Overall, 2539 (80.2%) of patients and 24,676 of controls had redeemed more than one prescription for antibiotics >3 years before their AML diagnosis/index date. Prior use of antibiotics was associated with a higher risk of AML (OR 1.2 (CI=1.1-1.3)). However as for infections, the association was only evident for sAML/tAML (OR 1.8 (CI=1.5-2.2)), whereas the risk of de novo AMLwas not increased (OR 1.0 (CI=0.9-1.1)).In a subgroup analysis of individual autoimmune diseases, only gastrointestinal disease was associated with de novo AML (GI autoimmune disease: de novo AML: OR 1.5 (CI=1.0-2.1), sAML/tAML: OR 1.5 (CI=0.9-2.7)). Of infections, only gastrointestinal infections were associated with de novo AML (de novo AML: OR 1.5 (CI=1.1-2.0), sAML/tAML: OR 1.8 (CI=1.1-2.9)).ConclusionThis large population-based study using high-quality data shows that use of antibiotics, infections, and autoimmune diseases are not per se associated with AML.Only gastrointestinal autoimmune disease and gastrointestinal infections were associated with increased risk of de novo AML. Though, we cannot rule out the possibility that infections or autoimmune diseases in the gastrointestinal tracts cause immune-related/inflammation-driven leukemogenesis, these findings are likely coincidental or explained by therapeutic immune-modulating agents increasing both risk of infections and AML.In summery, our results indicate that in patients without prior hematological disease or exposure to cytotoxic therapy, inflammation plays - if any - only a minor role in leukemogenesis. [Display omitted] DisclosuresØstgård:Pfizer: Other: Travel expences; The Danish Cancer Society: Research Funding. Nørgaard:Program for Clinical Research Infrastructure (PROCRIN): Research Funding. Pedersen:Program for Clinical Research Infrastructure (PROCRIN): Research Funding. Østgård:Lilly: Consultancy; Bristol-Myers Squibb: Consultancy; Pfizer: Consultancy; AbbVie: Consultancy. Schöllkopf:Pfizer: Other: Travel expences; Teva: Other: Travel expences; Karyopharm Therapeutics: Research Funding. Severinsen:ARIAD: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Jensen:The Dagmar Marshall Foundation: Research Funding; The Danish Acute Leukemia Group: Research Funding.

The role of vitamin D in selected autoimmune diseases.

The authors of recently published scientific papers are focusing increasingly often on the effect of vitamin D on immune processes. In the case of deficiencies of this vitamin, an imbalance in the immune system is observed, which is associated with the intensification of the inflammatory reaction in the body and the increased possibility of an autoimmune reaction. Therefore, due to the growing interest of scientists in the relationship between the effects of vitamin D and the development of autoimmune diseases, this paper considers the use of Vitamin D in autoimmune therapies. However, the mechanism of vitamin D on individual autoimmune diseases has not been elucidated so far, therefore there is a need for further research. The importance of maintaining normal plasma vitamin D levels to reduce the risk of developing autoimmune diseases has been demonstrated by the authors of other studies. They showed that vitamin D levels influenced the course, severity of symptoms and frequency of relapses of autoimmune thyroid disease, inflammatory bowel disease, and rheumatoid arthritis.

Lung Cancer Survival in Patients With Autoimmune Disease

Patients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown. To determine the association between autoimmune disease and lung cancer survival. Retrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020. Presence of autoimmune disease. Overall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group. Of the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease. Compared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.

Epigenetic fine-mapping: identification of causal mechanisms for autoimmunity.

Genome-wide association studies (GWAS) have identified genetic susceptibility loci for a variety of autoimmune and inflammatory diseases. These studies confirm the fundamental genetic basis of individual autoimmune diseases, and also point to shared etiological mechanisms across the spectrum of autoimmunity. While hundreds of genetic loci have been implicated in autoimmune diseases, the translation of individual susceptibility loci into specific molecular mechanisms for individual diseases remains difficult. This review highlights recent advances in the genetics of autoimmune disease, and the emerging use of epigenetic techniques to identify pathogenic cell types and causal molecular mechanisms of autoimmunity.

Low HDL Cholesterol and High Risk of Autoimmune Disease: Two Population-Based Cohort Studies Including 117341 Individuals.

HDL is quantitatively the most important lipoprotein in most species and mechanistic evidence points toward a role for HDL in normal immune function. We tested the hypothesis that concentrations of HDL cholesterol are associated with risk of autoimmune disease. From 2 studies of the general population-the Copenhagen General Population Study and the Copenhagen City Heart study-we included 107954 and 9387 individuals with baseline measurements of HDL cholesterol. These were followed with the national Danish Patient Registry from baseline in 2003-2015 or 1991-1994 through 2017, during which time 4078 and 1101 individuals developed autoimmune disease in the 2 studies. In the Copenhagen General Population Study, compared to individuals with HDL cholesterol ≥2.0 mmol/L (77 mg/dL), the multifactorially adjusted hazard ratios for any autoimmune disease were 1.06 (95% CI, 0.94-1.19) for individuals with HDL cholesterol of 1.5-1.99 mmol/L (58-77 mg/dL), 1.18 (95% CI, 1.04-1.35) for individuals with HDL cholesterol of 1.0-1.49 mmol/L (39-58 mg/dL), and 1.84 (95% CI, 1.52-2.22) for individuals with HDL cholesterol <1.0 mmol/L (39 mg/dL) (P for trend <0.001). These results were similar when excluding events within 5 years of baseline, in women and men separately, for events at baseline, irrespective of low-grade inflammation or triglyceride concentrations, for the apolipoprotein A1 part of HDL, and for more restrictive end point definitions. Finally, the Copenhagen City Heart Study provided independent confirmation. Low HDL cholesterol level is associated with high risk of autoimmune disease in individuals from the general population. Our observational findings cannot determine causality.

Bidirectional relationship between eating disorders and autoimmune diseases.

Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases. In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs. We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED. The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.

IL-27 Protects from Autoimmunity by Suppressing IL-17 Production and Promoting Treg Suppressor Functions

Abstract IL-27 has been implicated in the regulation of several autoimmune diseases including multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. However, a better mechanistic understanding of how IL-27 regulates individual autoimmune diseases is needed. Autoimmune gastritis involves chronic inflammation and tissue damage caused by self-reactive T cells and autoantibodies. Serious consequences of autoimmune gastritis include pernicious anemia and a significant increase in the risk of developing gastric cancer. We used a TCR transgenic mouse model (TxA23) in which mice develop autoimmune gastritis due to CD4+ T cells that express a transgenic TCR specific for a peptide expressed by parietal cells in the gastric mucosa. Disease in this model mimics many aspects of human disease including the development of autoantibodies and precancerous lesions. We recently discovered a critical role for IL-27 in regulating autoimmune gastritis. IL-27 deficient mice have more severe inflammation and tissue damage, and develop precancerous lesions much faster compared to control mice. Further analyses revealed that IL-27 expression suppressed IL-17A secretion by immune cells in vivo. In vitro we observed that IL-27 acts directly on autoreactive CD4+ T cells and reduced IL-17A secretion. Finally, IL-27 expression increased inhibitory receptors (LAG3, CD39, CD73, GITR, CD25) on CD4+FoxP3+ regulatory T cells (Tregs) and supported their ability to suppress autoreactive CD4+ T cells in vitro. These data elucidate an important role for IL-27 in protecting from autoimmune gastritis by suppressing IL-17A secretion and promoting suppressor functions of Tregs.

Context-specific effects of genetic variants associated with autoimmune disease.

Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms (SNPs)) has increased since genome-wide association studies (GWAS) became possible in 2007 and, for individual diseases, SNPs can now explain some 15–50% of genetic risk. GWAS have also shown that some 50% of the genetic risk factors for individual autoimmune diseases overlap between different diseases. Thus, shared risk factors may converge to pathways that, when perturbed by genetic variation, predispose to autoimmunity in general. This raises the question of what determines disease specificity, and suggests that identical risk factors may have different effects in various autoimmune diseases. Addressing this question requires translation of genetic risk factors to causal genes and then to molecular and cellular pathways. Since >90% of the genetic risk factors are found in the non-coding part of the genome (i.e. outside the exons of protein-coding genes) and can have an impact on gene regulation, there is an urgent need to better understand the non-coding part of the genome. Here, we will outline the methods being used to unravel the gene regulatory networks perturbed in autoimmune diseases and the importance of doing this in the relevant cell types. We will highlight findings in coeliac disease, which manifests in the small intestine, to demonstrate how cell type and disease context can impact on the consequences of genetic risk factors.

Vaccinations and risk of systemic lupus erythematosus and rheumatoid arthritis: A systematic review and meta-analysis.

In the past several years, more and more studies proposed some concerns on the possibly increased risk of autoimmune diseases in individuals receiving vaccinations, but published studies on the associations of vaccinations with risks of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) reported conflicting findings. A systematic review and meta-analysis was carried out to comprehensively evaluate the relationship between vaccinations and risk of SLE and RA. Pubmed, Web of Science and Embase were searched for observational studies assessing the associations of vaccinations with risks of RA and SLE. Two authors independently extracted data from those eligible studies. The quality of eligible studies was assessed by using the Newcastle-Ottawa Scale (NOS). The pooled relative risk (RR) with 95% confidence intervals (CIs) was used to measure the risk of RA and SLE associated with vaccinations, and was calculated through random-effect meta-analysis. Sixteen observational studies were finally considered eligible, including 12 studies on the association between vaccinations and SLE risk and 13 studies on the association between vaccinations and RA risk. The pooled findings suggested that vaccinations significantly increased risk of SLE (RR=1.50; 95%CI 1.05-2.12, P=0.02). In addition, there was an obvious association between vaccinations and increased risk of RA (RR=1.32; 95%CI 1.09-1.60, P=0.004). Meta-analysis of studies reporting outcomes of short vaccinated time also suggested that vaccinations could significantly increase risk of SLE (RR=1.93; 95%CI 1.07-3.48, P=0.028) and RA (RR=1.48; 95%CI 1.08-2.03, P=0.015). Sensitivity analyses in studies with low risk of bias also found obvious associations of vaccinations with increased risk of RA and SLE. This study suggests that vaccinations are related to increased risks of SLE and RA. More and larger observational studies are needed to further verify the findings above and to assess the associations of vaccinations with other rheumatic diseases.

Maternal autoimmune disease and birth defects in the National Birth Defects Prevention Study.

Little is known about the association between maternal autoimmune disease or its treatment and the risk of birth defects. We examined these associations using data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. Analyses included 25,116 case and 9897 unaffected control infants with estimated delivery dates between 1997 and 2009. Information on autoimmune disease, medication use, and other pregnancy exposures was collected by means of telephone interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for birth defects with five or more exposed cases; crude ORs and exact 95% CIs were estimated for birth defects with three to four exposed cases. Autoimmune disease was reported by 373 mothers (279 case and 94 control mothers). The majority of birth defects evaluated were not associated with autoimmune disease; however, a statistically significant association between maternal autoimmune disease and encephalocele was observed (OR, 4.64; 95% CI, 1.95-11.04). Eighty-two mothers with autoimmune disease used an immune modifying/suppressing medication during pregnancy; this was associated with encephalocele (OR, 7.26; 95% CI, 1.37-24.61) and atrial septal defects (OR, 3.01; 95% CI, 1.16-7.80). Our findings suggest maternal autoimmune disease and treatment are not associated with the majority of birth defects, but may be associated with some defects, particularly encephalocele. Given the low prevalence of individual autoimmune diseases and the rare use of specific medications, we were unable to examine associations of specific autoimmune diseases and medications with birth defects. Other studies are needed to confirm these findings. Birth Defects Research (Part A) 106:950-962, 2016. © 2016 Wiley Periodicals, Inc.

Management and Risk Reduction of Rheumatoid Arthritis in Individuals with Obstructive Sleep Apnea: A Nationwide Population-Based Study in Taiwan.

To explore associations between obstructive sleep apnea (OSA) and autoimmune diseases and evaluate whether OSA management reduces the incidence of autoimmune diseases. This was a retrospective cohort study using nationwide database research. The data was from 105,846 adult patients in whom OSA was diagnosed and recorded in the Taiwan National Health Insurance Research Database between 2002 and 2011 were the patients were analyzed retrospectively. Patients with antecedent autoimmune diseases were excluded. A comparison cohort of 423,384 participants without OSA served as age- and sex-matched controls. Multivariable Cox regression analysis was performed on both cohorts to compute risk of autoimmune diseases during follow-up. Time-dependent OSA treatment effect was analyzed among patients with OSA. There were no interventions. Among patients with OSA, overall risk for incident autoimmune diseases was significantly higher than that in controls (adjusted hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.66-2.27). Risk for individual autoimmune diseases, including rheumatoid arthritis (RA), Sjögren syndrome (SS), and Behçet disease, was significantly higher in patients with OSA than in controls (HRs [95% CI]: RA 1.33 [1.03-1.72, SS 3.45 [2.67-4.45] and Behçet disease 5.33 [2.45-12.66]). Increased risk for systemic lupus erythematosus (HR 1.00 [0.54-1.84]) and systemic sclerosis (HR 1.43 [0.51-3.96]) did not reach statistical significance. Patients with OSA receiving treatment had an overall reduced risk of RA and other autoimmune diseases (time-dependent HRs [95% CI]: 0.22 [0.05-0.94] and 0.51 [0.28-0.92], respectively). Patients with OSA are associated with higher risk for developing RA, SS, and Behçet disease. OSA management is associated with reduced risk of RA.