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Background: Observational studies have shown a link between autoimmune diseases and schizophrenia, with conflicting conclusions. Due to the existence of confounding factors, the causal link between autoimmune diseases and schizophrenia is still unknown., Method: We conducted a comprehensive Mendelian randomization (MR) analysis of schizophrenia and ten common autoimmune diseases in individuals of European descent using genome-wide association studies (GWASs). To evaluate the relationships between autoimmune diseases and schizophrenia, inverse variance weighted, MR-RAPS, Bayesian weighted MR, constrained maximum likelihood, debiased IVW, MR-Egger, and weighted median were utilized. Several sensitivity analyses were performed to ensure the reliability of the study's results., Results: Our findings reveal that genetically predicted ankylosing spondylitis is related to an increased risk of schizophrenia, whereas celiac disease, type 1 diabetes, and systemic lupus erythematosus are associated with a lower risk of schizophrenia. In the reverse MR analysis, our study indicated that genetically predicted schizophrenia is linked to higher risks of ankylosing spondylitis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, and psoriasis. Neither multiple sclerosis nor rheumatoid arthritis have been linked to schizophrenia, and vice versa., Conclusion: Despite contradicting some other observational reports, this study showed support for a causal link between autoimmune diseases and schizophrenia. To gain a better understanding of the mechanisms underlying the development of immune-mediated schizophrenia, additional research is required to identify potential mechanisms identified in observational studies., Competing Interests: Declarations Ethics approval and consent to participate The data used in our MR analysis is entirely from previously reported summary data. Therefore, neither patient consent nor ethical approval was necessary for the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Parvovirus B19 infection has been associated with various clinical entities including musculoskeletal manifestations and the development of different autoimmune diseases. The aim of our study is to examine the musculoskeletal manifestations associated with acute parvovirus B19 infection and the possible development of chronic autoimmune rheumatic diseases., Patients and Methods: Retrospective cohort study that included adult hospitalized patients diagnosed with an acute parvovirus B19 infection between 1 January 2021 and 1 February 2024. Subjects were followed-up for 6-12 months after hospitalization aiming to identify patients who developed chronic autoimmune rheumatic diseases., Results: The study included 23 patients diagnosed with acute parvovirus B19 infection. Patients were predominantly females (16, 69.6%) with mean age at diagnosis of 39.3 ± 13.11 years. Most patients were Jewish (15, 65.2%). The two most common acute symptoms were fever (82.6%) and myalgia (56.5%). Polyarthritis was present only in three patients (13%) and all of them had wrists involvement. Anti-nuclear antibodies and rheumatoid factor were the most common autoantibodies present with equal prevalence each (13%). Five patients were treated with prednisone during the acute phase (21%), two (8.7%) of them needed drug escalation and were subsequently treated with hydroxychloroquine and methotrexate. One patient developed systemic lupus erythematosus during the first 6 months of follow-up., Conclusion: Musculoskeletal manifestations developing during acute parvovirus B19 are usually self-limited with only a small minority of patients developing chronic autoimmune diseases. It is crucial to differentiate self-limited manifestations related to acute parvovirus B19 from idiopathic autoimmune diseases aiming to avoid unnecessary immunosuppressive therapy., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Non-Hodgkin lymphoma (NHL) is one of the most common haematologic malignancies in the world. Despite substantial efforts to identify causes and risk factors for NHL, its aetiology is largely unclear. Autoimmune diseases have long been considered potential risk factors for NHL. We carried out Mendelian randomisation (MR) analyses to examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of NHL., Methods: Two-sample MR was performed using publicly available summary statistics from cohorts of European ancestry. For NHL and four NHL subtypes, we used data from UK Biobank, Kaiser Permanente cohorts, and FinnGen studies., Results: Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92-0.98, p = 5 × 10 -3 , and OR 0.92, 95% CI: 0.85-0.99, p = 2.8 × 10 -2 , respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk., Conclusion: These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Study Question: Is there an association between premature ovarian insufficiency (POI) and severe autoimmune diseases before and after POI diagnosis?, Summary Answer: Women with POI had at least one hospital-treated autoimmune disorder preceding POI diagnosis 2.6 times more often compared with matched female controls, and a 2- to 3-fold risk for these diseases for several years after POI diagnosis., What Is Known Already: It has been suggested that autoimmunity is an important factor in the pathogenesis of POI. Estimations of the prevalence of POI cases with autoimmune origin have ranged from 4% to 50%., Study Design, Size, Duration: This population-based registry study included 3972 women diagnosed with spontaneous POI between 1988 and 2017 and 15 708 female population controls and used both case-control and cohort analysis. Autoimmune disease diagnoses were evaluated from childhood until the end of the year 2017., Participants/materials, Setting, Methods: Women with POI were identified from the reimbursement registry of the Finnish Social Insurance Institution by their right to hormone replacement therapy (HRT). Four female population controls matched by age and municipality of residence were searched for each POI case to form a reference cohort. Women with a history of cancer or bilateral oophorectomy were excluded. Severe autoimmune disorder diagnoses for the years 1970-2017 were identified from the Hospital Discharge Registry. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using binary logistic regression for cases of having any, or one or more, specific autoimmune diseases preceding the index date (the date when reimbursement for HRT was granted for the POI) among women with POI as compared to controls. Standardized incidence ratios (SIR) with 95% CIs for getting diagnosed with an autoimmune disease after the index date in 3-year follow-up periods among women with POI (who did not have these diseases prior to the index date) were also calculated. The expected numbers of autoimmune disease cases were based on the incidence of first-onset severe autoimmune disease among the controls., Main Results and the Role of Chance: The prevalence of having at least one severe autoimmune disease in women with POI was 5.6% (n = 233), with an OR of 2.6 (95% CI 2.2, 3.1) when compared to population controls. Women with POI had an increased prevalence of several specific autoimmune diseases prior to the index date compared to controls: polyglandular autoimmune diseases (OR 25.8, 95% CI 9.0, 74.1), Addison's disease (OR 22.9, 95% CI 7.9, 66.1), vasculitis (OR 10.2, 95% 4.3, 24.5), systemic lupus erythematosus (OR 6.3 95% CI 4.2, 20.3), rheumatoid arthritis (OR 2.3, 95% CI 1.7, 3.2), sarcoidosis (OR 2.3, 95% CI 1.2, 4.5), inflammatory bowel diseases (OR 2.2, 95% CI 1.5, 3.3), and hyperthyroidism (OR 1.9, 95% CI 1.2, 3.1); whereas the prevalence of diabetes type 1 and ankylosing spondylitis did not differ between the women with POI and the reference cohort. The SIRs for being diagnosed for the first time with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI 2.3, 3.4), during the first three years after POI diagnosis, decreasing gradually to 1.3 (1.1, 1.6) after 12 years., Limitations, Reasons for Caution: This study only included autoimmune disorders diagnosed in specialized health care; hence, the overall prevalence of autoimmune disorders in women with POI may be higher., Wider Implications of the Findings: Severe autoimmune diseases have a strong association with POI, suggesting that immunological mechanisms play a pivotal role in POI. Future studies should focus on specific autoimmune mechanisms behind POI, from both preventive and curative perspectives., Study Funding/competing Interest(s): This work was financially supported by Oulu University Hospital. S.M.S. received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. H.S. received grants from the Finnish Menopause Society, the Oulu Medical Research Foundation, the Finnish Research Foundation of Gynecology and Obstetrics, UniOGS graduate school, The Finnish Medical Society Duodecim, Orion Research Foundation, and the University of Oulu Scholarship Fund. M.-M.O. received a grant from the Sakari Alhopuro Foundation and the Finnish Diabetes Research Foundation. None of the funders had any involvement in the study design or its execution or reporting. The authors do not have any competing interests to report., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Design: Nationwide epidemiological open cohort study., Objectives: To evaluate whether individuals with traumatic spinal cord injury (TSCI) are more prone to develop autoimmune diseases compared to a general non-TSCI population., Setting: Danish public national registries., Methods: An open nationwide cohort, including individuals born in Denmark from or alive during 1945-2018 was collected and the study period was 1980-2018. Poissons Log-linear regression estimated the incidence rate ratio (IRR) for developing eight groups of autoimmune diseases. A dose-response relationship based on the cervical/thoracic level of injury was assessed by stratification., Results: The cohort included 3,272 individuals with TSCI and 4.8 million background individuals, accounting for 50,865 and 140 million person-years respectively. The TSCI population had an overall IRR of 1.81 (95% CI, 1.59 to 2.05) of getting any autoimmune disease. Subgroup analysis found positive associations for; a) Other neurologic IRR 5.19 (95% CI, 2.79 to 9.65), b) multiple sclerosis IRR 3.70 (95% CI, 2.54 to 5.40), c) Dermatologic IRR 2.57 (95% CI, 1.86 to 3.55), d) Type 1 diabetes mellitus IRR 2.01 (95% CI, 1.54 to 2.61), e) Systemic 1.92 (95% CI, 1.44 to 2.55), and f) Gastroenterologic IRR 1.42 (95% CI, 1.05 to 1.92). Cervical levels of TSCI showed an IRR of 1.70 (95% CI, 1.43 to 2.02), while thoracic levels had an IRR 1.98 (95% CI, 1.63 to 2.39)., Conclusions: TSCI may be an individual risk factor of developing an autoimmune disease. There does not appear to exist a dose-response relationship from the level of injury., Sponsorship: None., (© 2024. The Author(s).)

Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against factor VIII, with a high mortality risk. It should be suspected in subjects with abnormal bleedings, especially subcutaneous bleed associated with prolonged activated partial thromboplastin time (aPTT). AHA is often idiopathic but is associated with autoimmune diseases, malignancies, pregnancy and postpartum period or drugs. Treatment is based on haemostatic agents as by-passants agents such as factor VIIa and activated prothrombine concentrate complex or recombinant porcine factor VIII for severe bleeding. Eradication of inhibitor should be established as soon as the diagnosis is confirmed with steroid alone often associated with cytotoxic agents or rituximab, depending on FVIII activity and inhibitor titer. The purpose of this review is to summarize the epidemiology, etiopathogenesis, diagnosis, treatment of AHA and discuss current recommendations., (Copyright © 2024. Published by Elsevier Masson SAS.)

Purpose: The current study queries the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) registry for data on the epidemiology, work-up, and management patterns of autoimmune orbital inflammation., Methods: Analysis and description of patient data from the IRIS registry between 2013 and 2019 reviewing patients with autoimmune or idiopathic orbital inflammation with filters based on International Classification of Disease (ICD) and Current Procedural Terminology (CPT) codes. Patients with thyroid eye disease, orbital cellulitis, and orbital abscess were excluded., Main Outcome Measures: Demographic descriptions included gender, age, geographic region, and treatment. Sub-analysis was performed by assessing rates of imaging, biopsy, lab work-up, and diagnostic categories., Results: In a final cohort of 20,584 patients, the mean age of onset of orbital inflammation was 51.7 years; 67% female; and 63% Caucasian, 21% unknown, 12% Black, 2.6% Asian, and 1.5% other. Only 49 had imaging, 78 had laboratory work-up, and 1,411 had biopsy codes. Treatment results showed 166 patients receiving antibiotics, 224 patients receiving steroids, and 35 patients receiving both., Conclusions: This study assessed the epidemiology, diagnostic patterns, and treatment patterns for orbital inflammation through the AAO IRIS registry. Practise patterns suggest a relatively low overall rate of imaging and laboratory studies compared to biopsies, although this certainly under-represents the actual number of imaging and laboratory studies and exemplifies the inherent imprecision of using a large database. However, the methodology of this study provides a framework of approaching the IRIS registry for oculoplastic research.

Purpose: This review aimed to investigate the prevalence of hypertension and cardiovascular (CV) complications in various inflammatory and autoimmune diseases (IAD)., Recent Findings: Despite recent improvements in the management of IAD, patients with IAD still have an increased CV mortality and CV complications, mostly related to CV risk factors such as hypertension and inflammation. We systematically searched MEDLINE and EMBASE libraries for controlled studies involving hypertension and CV complications in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis including psoriatic arthritis (PsA), Sjogren's syndrome (SS), or antineutrophil cytoplasmic antibody-associated vasculitis (AAV) between January 2000 and March 2022. We extracted data on the prevalence of hypertension and CV complications. Then, random-effects meta-analyses and exploratory multivariate meta-regression were performed to explore factors related to the prevalence of hypertension. Of 2726 studies screened, 122 were selected for the meta-analysis. The prevalence of hypertension was higher among patients with IAD than controls, with an overall unadjusted odds ratio (OR) [95% confidence interval] of 1.67 [1.58-1.76] and an adjusted OR of 1.36 [1.24-1.50]. All diseases were found to be associated with increased risk of hypertension: SLE, adjusted OR 3.40 [1.93-6.00]; psoriasis, OR 1.32 [1.16-1.51]; PsA, OR 1.49 [1.15-1.94]; RA, OR 1.28 [1.04-1.58]; SS, OR 2.02 [1.19-3.44]. Age and female sex were significantly associated with hypertension in patients with IAD. The risk of CV complications was increased: ischemic heart disease, adjusted OR 1.38 [1.21-1.57]; cerebrovascular disease, OR 1.37 [1.03-1.81]; heart failure, OR 1.28 [1.05-1.55]; atherosclerotic plaques presence, OR 2.46 [1.84-3.29]. The prevalence of hypertension and CV complications is higher among patients with IAD. Screening and management of hypertension appears to be of paramount importance in these patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The percentage of autoimmune diseases in Western countries is approximately 8% of the total population. Despite numerous studies indicating an increase in prevalence and incidence over the past two decades, autoimmune vestibular disorders seem to be underdiagnosed, primarily due to the lack of a definitive test capable of identifying the specific antigen of the inner ear. Autoimmune inner ear disease (AIED) is defined as a rapidly progressive and often fluctuating bilateral neurosensorial hearing loss that develops over a period of weeks or months. AIED can affect only the inner ear or be part of systemic diseases such as granulomatosis with polyangiitis, Cogan's syndrome, systemic lupus erythematosus, polyarteritis nodosa, or relapsing polychondritis, among others. Our main objective was to conduct a study on the presence of antiphospholipid antibodies (aPL) in patients with AIED seen in a specialised clinic., Methods: We designed an observational retrospective study in which we selected patients from a total group of 55 with AIED referred to the Autoimmune Diseases Clinic, those with confirmed positivity for antiphospholipid antibodies, and described their clinical, analytical, and epidemiological characteristics., Results: We found a prevalence of 29% positivity for antiphospholipid antibodies, with lupus anticoagulant (LA) being the most frequently detected, followed by anticardiolipin (aCL) and anti-beta2 glycoprotein (anti-B2GP). Double positivity was observed in 25% of patients. The main clinical manifestations were bilateral hearing loss, vestibular symptoms, and tinnitus. Only 25% of patients experienced audiometric improvement during the course of the disease., Conclusions: We emphasise the importance of identifying the presence of aPL in AIED, enabling the establishment of appropriate and specific therapeutic management to prevent audiometric deterioration.

Background: Early identification of risk factors for adverse COVID-19 progression in patients with autoimmune diseases is crucial for patient management, but data on the Chinese population are scarce., Objectives: The purpose of this study was to identify predictors of severe COVID-19 in patients using blood cell ratios, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and other inflammatory markers., Methods: A retrospective study of 855 patients (746 females; median age 49 years) with autoimmune diseases and concurrent COVID-19 was conducted from December 2022 to February 2023 at the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University. Disease severity was assessed according to the 8th edition of the National Health Commission of the People's Republic of China's COVID-19 Diagnosis and Treatment Guidelines. The clinical classification criteria group mild and moderate cases as nonsevere cases and severe and critical cases as severe cases. A multivariate logistic regression model was established to evaluate the relationships between COVID-19 severity and demographic characteristics, comorbidities, medication use, and laboratory findings., Results: The PLR, NLR, and SII were significantly greater in the severe COVID-19 group than in the nonsevere group (all P < 0.05). In addition to classical independent clinical risk factors, increases in the PLR (OR: 1.004, 95 % CI: 1.001∼1.007, p = 0.001), NLR (OR: 1.180, 95 % CI: 1.041∼1.337, p = 0.010), and SII (OR: 0.999, 95 % CI: 0.998∼1.000, p = 0.005) were identified as risk factors for severe COVID-19 in patients with autoimmune diseases. After adjusting for clinical risk factors, the PLR (AUC: 0.592 vs. 0.865; P < 0.05), NLR (AUC: 0.670 vs. 0.866; P < 0.05), and SII (AUC: 0.616 vs. 0.864; P < 0.05) demonstrated higher predictive values., Conclusion: Early prediction of severe COVID-19 in patients with autoimmune diseases can be achieved using the NLR, PLR, and SII., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: An autoimmune component in the cause of sarcoidosis has long been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause are limited., Research Question: Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis?, Study Design and Methods: We conducted a case-control-family study (2001-2020). Patients with sarcoidosis (N = 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N = 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95% CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs., Results: Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7% vs 4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95% CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95% CI, 0.97-3.65), thyroiditis (OR, 1.72; 95% CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95% CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95% CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95% CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95% CI, 1.00-1.93)., Interpretation: This study showed that IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cysteine cathepsins are proteolytic enzymes crucial in various physiological and pathological processes, primarily operating within lysosomes. Their functions include protein degradation, immune system regulation, and involvement in various diseases. While some cysteine cathepsins play important roles in the immune system, their connection to autoimmune diseases remains unclear. This study proposes using Mendelian randomization to explore the causal relationship between cysteine cathepsins and autoimmune diseases. Single nucleotide polymorphisms (SNPs) for cysteine cathepsins were obtained from a publicly available genome-wide association study (GWAS) dataset, while outcome SNP data were sourced from 10 separate GWAS datasets. Mendelian randomization (MR) analysis employed the Wald ratio (WR) and inverse variance weighted (IVW) approach as primary methods, supplemented by the weighted median and MR-Egger methods. Heterogeneity was assessed using Cochran Q test, and sensitivity analysis was conducted using the MR-PRESSO method. The association strength between exposure and outcome was evaluated using odds ratios (OR) with 95% confidence intervals (CI). The study identified a potential positive correlation between elevated cathepsin B and psoriasis (Wald ratio OR = 1.449, 95% CI: 1.053-1.993, P = .0227). Elevated cathepsin F was potentially linked to ulcerative colitis (WR OR = 1.073, 95% CI: 1.021-1.127, P = .0056), ankylosing spondylitis (WR OR = 1.258, 95% CI: 1.082-1.463, P = .0029), and primary biliary cholangitis(PBC) (WR OR = 1.958, 95% CI: 1.326-2.889, P = .0007). Conversely, cathepsin H appeared protective against celiac disease (WR OR = 0.881, 95% CI: 0.838-0.926, P = 6.5e-7), though elevated levels may increase the risk of type 1 diabetes (IVW OR = 1.121, 95% CI: 1.053-1.194, P = .0003) and PBC (WR OR = 1.792, 95% CI: 1.062-3.024, P = .0288). Cathepsin Z was also associated with an increased risk of type 1 diabetes (IVW OR = 1.090, 95% CI: 1.006-1.181, P = .0349). The MR analysis suggests potential risks of cathepsin B with psoriasis, cathepsin F with ulcerative colitis, ankylosing spondylitis, and PBC, and cathepsin Z with type 1 diabetes. Conversely, cathepsin H may protect against celiac disease but could increase the risk of type 1 diabetes and PBC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden., Methods: Autoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000-2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models., Results: During the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13-7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76-15.65) and hypothyroidism (HR 3.74, 95% CI 1.14-12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64-23.55) for ANA positive individuals., Conclusions: Individuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up., (© 2024. The Author(s).)

Newly emerging evidence indicates that body mass index (BMI) is a potential risk factor for autoimmune diseases (ADs). Nevertheless, the exact causal connection between ADs and BMI in children remains uncertain. To investigate the relationship between BMI in children and ADs, a 2-sample Mendelian randomization (MR) analysis was conducted. In this analysis, several regression methods were utilized, including the inverse-variance weighted (IVW), weighted mode, weighted median, and MR-Egger regression. Publicly available summary statistics datasets from meta-analyses of genome-wide association studies (GWAS) were employed, specifically focusing on BMI in children of European descent (n = 39,620) from the UK Biobank (ebi-a-GCST90002409) as the exposure group. The outcomes were derived from individuals included in the Finnish biobank study FinnGen, with 42,202 cases and 176,590 controls representing the ADs group (finngen&#95;R5&#95;AUTOIMMUNE). For instrumental variables, we carefully selected 16 single nucleotide polymorphisms (SNPs) from GWAS on BMI in children. Our analysis implemented the IVW method, which demonstrated supporting evidence for a causal association between BMI in children and ADs. The results indicated a significant effect with a beta coefficient of 0.22, standard error (SE) of 0.05, odds ratio (OR) of 1.25, and a 95% confidence interval (CI) ranging from 1.13 to 1.38, with a P-value of <.05. We also utilized the weighted median method, which yielded similar findings to the IVW method. The OR estimates from the weighted median analysis showed a beta coefficient of 0.20, SE of 0.06, OR of 1.22, and a 95% CI ranging from 1.08 to 1.36, with a P-value of <.05. No significant association was observed in the MR-Egger and Weighted mode analyses. The findings from the MR analysis suggest that there is evidence supporting a potential causal link between BMI in children and an increased susceptibility to ADs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The global SARS-CoV-2 pandemic significantly altered lifestyles, access to healthcare, and social interactions, introducing unprecedented physical and psychological stress all over the world. This study explores the relationship between psychological stress, vitamin D (Vit-D) levels, and autoimmune connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis., Methods: The analysis was based on over one million patient data points derived from anti-nuclear antibody (ANA) testing conducted both before and during the COVID-19 pandemic 2017-2021. In a subset of patients, longitudinal data were collected bi-yearly to yearly over 5-8 years using the same three-month criteria. The dataset was analyzed using GraphPad Prism9 using paired t-tests or ordinary one-way ANOVA with a significance threshold of p < 0.05 to ensure robust correlations between the variables., Results: Data indicated that Vit-D levels peaked between 2017 and 2019 before declining, while ANA data demonstrated a rise in autoimmune connective tissue disease cases during the pandemic, reaching a peak in 2021. A clear correlation was observed, with autoimmune disease incidence increasing as Vit-D levels decreased. In-depth case analysis revealed that declining Vit-D levels preceded higher ANA titers and increased autoimmune disease severity, whereas improvements in Vit-D levels were associated with reduced ANA titers and less severe disease manifestations., Conclusions: The findings suggest that maintaining mental health and ensuring adequate Vit-D supplementation could be essential strategies for mitigating autoimmune disease risks and maintaining immune stability, particularly in pandemic scenarios. Clinically, these results underscore the need for early interventions targeting both psychological well-being and Vit-D levels to reduce the burden of autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alobaid and Alqabandi.)

Problem: Research has suggested a link between recurrent pregnancy loss (RPL) and cell-mediated immunity dysregulation. We aimed to determine if a history of RPL is associated with diagnosis of a cell-mediated autoimmune condition (AIC)., Method of Study: A retrospective cohort study was conducted using the TriNetX research network. The RPL group had ≥3 spontaneous or missed abortions. Controls had at least one pregnancy but no diagnosis of RPL. Propensity score matching was used for age, race, and ethnicity. Z-test and relative risk analysis investigated the relationship between RPL and subsequent AIC diagnoses., Results: One hundred twenty-eight thousand three hundred seventy-six patients were included in each cohort. RPL was associated with an increased risk for an AIC composite (RR 1.60, 95% CI [1.51, 1.69]), Crohn's disease, Graves' disease, Hashimoto's thyroiditis, multiple sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and ulcerative colitis, but not psoriatic arthritis., Conclusions: Using a large research database of patients with RPL, we were able to demonstrate that an antecedent diagnosis of RPL is associated with increased risk of subsequent diagnosis of an AIC, often between 1 and 10 years after RPL., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980-2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots&#95;16918786403110/e-Figure5. While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and nongenetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Patients with atopic dermatitis (AD) are at increased risk of atopic and non-atopic comorbidities. In fact, the Hanifin and Rajka criteria include allergic and infectious comorbidities as a minor criterion. Despite the well-recognized list of comorbidities, the past 15 years greatly expanded the list of recognized comorbidities of AD. This narrative review focuses on comorbidities of AD using a mnemonic, VINDICATE-P: vascular/cardiovascular, infectious, neoplastic and neurologic, degenerative, iatrogenic, congenital, atopic and autoimmune, traumatic, endocrine/metabolic, and psychiatric. The comorbidities of AD vary by age. More research is needed into the mechanisms of comorbidities and optimal screening strategies in AD patients., Competing Interests: Disclosure J.I. Silverberg has received honoraria as a consultant and/or advisory board member for Abbvie, Alamar, Aldena, Amgen, AObiome, Apollo, Arcutis, Arena, Asana, Aslan, Attovia, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristell-Meyers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, FIDE, Galderma, GlaxoSmithKline, Incyte, Inmagene, Invea, Kiniksa, Leo Pharma, Merck, My-Or Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, TARGET-RWE, Teva, Union, UpToDate; speaker for Abbvie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; institution received grants from Galderma, Incyte, Pfizer. Nanette Silverberg has received honoraria as a consultant, speaker, and/ or advisory board member for Incyte, Leo. Novan, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica Pharmaceuticals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pulmonary hypertension is a rare, incurable, and progressive disease. Although there is increasing evidence that immune disorders, particularly those associated with connective tissue diseases, are a strong predisposing factor in the development of pulmonary arterial hypertension (PAH), there is currently a lack of knowledge about the detailed molecular mechanisms responsible for this phenomenon. Exploring this topic is crucial because patients with an immune disorder combined with PAH have a worse prognosis and higher mortality compared with patients with other PAH subtypes. Moreover, data recorded worldwide show that the prevalence of PAH in women is 2× to even 4× higher than in men, and the ratio of PAH associated with autoimmune diseases is even higher (9:1). Sexual dimorphism in the pathogenesis of cardiovascular disease was explained for many years by the action of female sex hormones. However, there are increasing reports of interactions between sex hormones and sex chromosomes, and differences in the pathogenesis of cardiovascular disease may be controlled not only by sex hormones but also by sex chromosome pathways that are not dependent on the gonads. This review discusses the role of estrogen and genetic factors including the role of genes located on the X chromosome, as well as the potential protective role of the Y chromosome in sexual dimorphism, which is prominent in the occurrence of PAH associated with autoimmune diseases. Moreover, an overview of animal models that could potentially play a role in further investigating the aforementioned link was also reviewed., Competing Interests: None.

Objective: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs)., Methods: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models., Results: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89-6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04-5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively., Conclusion: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals., (© 2024. The Author(s).)

Aim: To modify the antibody prevalence in epilepsy (APE) score of children with suspected autoimmune central nervous system disease with seizures., Methods: We retrospectively analysed the cerebrospinal fluid of 157 children (aged 0-18 years) with suspected autoimmune central nervous system disease for antineuronal antibodies in our laboratory from 2016 to 2023. Participants were randomly divided into the development cohort (n = 79, 35 females; median 7 years, SD 4 years 7 months, range 4-11 years) and validation cohort (n = 78, 28 females; median 7 years, SD 4 years 5 months, range 4-12 years). A paediatric antibody prevalence in seizure (PAPS) score was created for one cohort and evaluated in the other. Seven variables were selected through univariate and multivariate analysis to create a PAPS score., Results: One hundred and fifty-seven children who fulfilled the inclusion criteria were enrolled; 49 tested positive for antineuronal antibodies. The sensitivity and specificity of an APE score of 4 and greater were 92% and 22.2% respectively; the sensitivity and specificity of a PAPS score of 2.5 and greater were 83.3% and 77.8% respectively. The area under the curve was 0.832 (95% confidence interval = 0.743-0.921), which was significantly better than that for the APE score (p < 0.001)., Interpretation: The APE score had high sensitivity but low specificity in children. The PAPS score may be useful for determining the need for antineuronal antibody testing., What This Paper Adds: The antibody prevalence in epilepsy (APE) score had high sensitivity but low specificity in children. The sensitivity and specificity of the paediatric antibody prevalence in seizure (PAPS) score were 83.3% and 77.8% respectively. There were significant differences in the area under the curve for the APE and PAPS scores., (© 2024 Mac Keith Press.)

Background and Aim: Patients with autoimmune inflammatory rheumatic disease (AIIRD) are at higher risk of severe infections because of their underlying diseases and immunosuppression. Our objective was to elucidate the epidemiological and clinical characteristics of patients with AIIRD presenting with COVID-19 and their relation to disease severity. We explored whether variables, including underlying diagnosis, disease-modifying antirheumatic drugs (DMARDs) and COVID-19 vaccine status, were associated with more severe forms of COVID-19 infection., Methods: Between 1 January 2020 and 30 June 2022, 151 patients with AIIRD and COVID-19 infection were analysed using a binary regression model and a multinomial regression model., Results: The average age was 61.5 years, and average Charlson Comorbidity Index (CCI) was 2.1; 106 (70.2%) patients were diagnosed with rheumatoid arthritis (RA), and 70 (46.4%) patients were receiving prednisolone. In the multivariable logistic regression model, ages between 50 and 69 years (odds ratio (OR) = 5.85; 95% confidence interval (CI) = 1.35-25.25) and older than 70 years (OR = 5.29; 95% CI = 1.21-23.14), prior prednisolone treatment (OR = 7.09; 95% CI = 2.63-19.11) and vaccination status including one and two doses (OR = 0.19; 95% CI = 0.05-0.69) and three and four doses (OR = 0.09; 95% CI = 0.02-0.35) were all statistically significant factors related to changes in the severity level of COVID-19., Conclusion: Severity of COVID-19 infection in patients with AIIRD is affected by age, background steroid use and vaccination status. Factors including sex, comorbidity, diagnosis of AIIRDs and use of DMARDs, including conventional synthetic, biologics and targeted DMARDs, were not significantly associated with COVID-19 severity., (© 2024 Royal Australasian College of Physicians.)

Objective: We investigated the baseline DMARD use and post-acute sequelae of COVID-19 (PASC) risk among patients with systemic autoimmune rheumatic diseases (SARDs)., Methods: Patients with SARDs and confirmed COVID-19 infection at Mass General Brigham completed a survey ≥28 days after a positive PCR/antigen test to prospectively investigate their COVID-19 courses. We investigated DMARD use at COVID-19 onset and PASC risk. PASC was defined as any COVID-19 symptom that persisted for ≥28 days. We used logistic regression to estimate the odds ratios (OR) for PASC by DMARD class. We also used restricted mean survival time to determine the difference in symptom-free days by DMARD class in the 28-day period after infection., Results: We analysed 510 patients with SARDs and COVID-19 from 11 March 2021 to 17 June 2023; 202 (40%) developed PASC. CD20 inhibitor (CD20i) users had significantly higher odds of developing PASC vs conventional synthetic DMARD (csDMARD) users [adjusted OR (aOR) 2.69 (95% CI 1.23, 5.88)]. IL-12/23, IL-17A or IL-23 inhibitor (IL-12/23i, IL-17Ai, IL-23i) users also had significantly higher odds of PASC [aOR 3.03 (95% CI 1.08, 8.49)]. CD20i users had significantly fewer symptom-free days vs csDMARD users [aOR -4.12 (95% CI -7.29, -0.94)]., Conclusion: CD20i users had significantly higher odds of PASC and fewer symptom-free days over the 28 days following COVID-19 diagnosis compared with csDMARD users. Further research is needed to investigate whether PASC risk in CD20i users may be due to prolonged infection or other immune mechanisms. The association of IL-12/23i, IL-17Ai and IL-23i with PASC calls for additional study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study compared opioid prescribing among ambulatory visits with systemic autoimmune/inflammatory rheumatic diseases (SARDs) or without and assessed factors associated with opioid prescribing in SARDs., Methods: This cross-sectional study used the National Ambulatory Medical Care Survey between 2006 and 2019. Adult (≥18 years) visits with a primary diagnosis of SARDs, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or systemic lupus erythematosus were included in the study. Opioid prescribing was compared between those with vs without SARDs using multivariable logistic regression accounting for the complex survey design and adjusting for predisposing, enabling, and need factors within Andersen's Behavioral Model of Health Services Use. Another multivariable logistic regression examined the predictors associated with opioid prescribing in SARDs., Results: Annually, an average of 5.20 million (95% confidence interval [CI] 3.58-6.82) visits were made for SARDs, whereas 780.14 million (95% CI 747.56-812.72) visits were made for non-SARDs. The SARDs group was more likely to be prescribed opioids (22.53%) than the non-SARDs group (9.83%) (adjusted odds ratio [aOR] 2.65; 95% CI 1.68-4.18). Among the SARDs visits, patient age from 50 to 64 (aOR 1.95; 95% CI 1.05-3.65 relative to ages 18-49) and prescribing of glucocorticoids (aOR 1.75; 95% CI 1.20-2.54) were associated with an increased odd of opioid prescribing, whereas private insurance relative to Medicare (aOR 0.50; 95% CI 0.31-0.82) was associated with a decreased odds of opioid prescribing., Conclusion: Opioid prescribing in SARDs was higher compared to non-SARDs. Concerted efforts are needed to determine the appropriateness of opioid prescribing in SARDs., (© 2024 American College of Rheumatology.)

Background: Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood., Objective: This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood., Study Design: We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses., Results: The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14)., Conclusion: Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies in epidemiology have indicated a link between chronic obstructive pulmonary disease (COPD) and various autoimmune conditions.This study aimed to investigate the potential causal link between nine autoimmune diseases with a genetic basis and COPD using a two-sample Mendelian randomization (MR) analysis., Method: To test the impact of susceptibility to immune-related outcomes on genetic prediction of COPD risk, we used pooled statistics from the largest genome-wide association study (GWAS) in Europe in a two-sample MR setting.Genetic data for type 1 diabetes, hypothyroidism, systemic lupus erythematosus, and primary biliary cirrhosis were obtained from the European Bioinformatics Institute (EBI), while data for multiple sclerosis and primary sclerosing cholangitis were extracted from the Integrative Epidemiology Unit (IEU) database. Additionally, genetic data for ulcerative colitis, rheumatoid arthritis, and celiac disease were also collected.These nine autoimmune diseases and the COPD cohort from the UK Biobank (1605 cases and 461,328 controls) were analyzed separately as exposure and outcome.Our primary method for the initial screening was inverse variance weighting (IVW).The MR-Egger regression test assessed multivariate validity, while the Cochran's Q test examined heterogeneity.To ensure the reliability of the findings, a leave-one-out analysis was conducted., Result: IVW discovered proof of type 1 diabetes (OR = 1.0003; 95 % CI = 1.0000-1.0005; P = 0.046), hypothyroidism (OR = 1.0004; 95 % CI = 1.0001-1.0008; P = 0.0263), celiac disease (OR = 1.0002; 95 % CI = 1.0000-1.0004; P = 0.0168) and systemic lupus erythematosus (OR = 1.0002; 95 % CI = 1.0000-1.0004; P = 0.049) were significantly linked to the heightened risk of COPD with no signs of variation or pleiotropy.Even after accounting for potential confounding factors like smoking, the correlation remained robust.Additionally, our research found that the IVW method did not indicate any causal link between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis (all P >0.05)., Conclusion: This research discovered that individuals with type 1 diabetes, hypothyroidism, celiac disease, and systemic lupus erythematosus have a higher likelihood of developing COPD.Additionally, this research revealed no connection between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest J.S.B. has received consulting fees from Dexcel Pharma for work unrelated to the current study. The other authors declare no conflicts of interest.

Competing Interests: Conflicts of interest None to declare.

Primary adrenal insufficiency (PAI) is a rare medical condition, characterized by a deficiency in adrenal hormones. Although rare, PAI is a life-threatening disease requiring prompt recognition and treatment. However, symptoms of PAI are often non-specific and diagnosis can be challenging, causing frequent diagnostic delays. In adults, autoimmunity is the most common cause of PAI in industrialized countries, whereas in children, the most frequent etiology is represented by congenital defects of steroidogenesis and, in particular, by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. A few recent case series from different countries have reported that autoimmunity is the second most common etiology of PAI in the pediatric age group. However, data on autoimmune PAI in children are still scant and the exact epidemiology, clinical manifestations, and long-term outcomes of this condition have yet to be defined. The scope of this review is to summarize the current knowledge on the etiology, presentation, and treatment of autoimmune PAI in childhood and to increase physicians' awareness of the signs that should raise an early suspicion of this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NI declared a shared affiliation with the authors to the handling editor at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Capalbo, Esposito, Gaeta, Lorello, Vasaturo, Di Mase and Salerno.)

Previous studies have suggested a possible link between autoimmune diseases and graft dysfunction; however, a causal link remains unclear. Exposure factors were set as 13 autoimmune diseases, and outcomes were set as graft dysfunction. Mendelian randomization was used to analyze the causal link between exposure and outcome. Alopecia areata and asthma were linked to graft dysfunction (odds ratio 0.828; 95% confidence interval 0.699-0.980; P = .029; odds ratio 1.79; 95% confidence interval 1.069-2.996; P = .027). At the same time, primary sclerosing cholangitis was found to be heterogeneous as an exposure factor (P = .009), but no heterogeneity or pleiotropy was found in other exposure factors. Our preliminary findings show 2 autoimmune diseases as risk factors for graft dysfunction, 1 autoimmune disease as a protective factor for graft dysfunction and the mechanisms remain to be understood., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Numerous observational and retrospective studies have demonstrated an association between Autoimmune Thyroiditis (AIT) and various systemic Autoimmune Diseases (AIDs). However, the causal relationship between them remains uncertain. This study aims to investigate the causal link between AIT and diverse types of AIDs utilizing the Mendelian Randomization (MR) method., Method: We assessed the causal relationship between AIT and eight prevalent AIDs. Summary statistics from genome-wide association studies (GWAS) were sourced from the FinnGen biobank and IEU Open GWAS database. Two-sample MR analyses were conducted, with the primary statistical approach being the Inverse Variance Weighting (IVW) method. This was complemented by a series of sensitivity analyses, and the robustness of the findings was evaluated through the estimation of heterogeneity and pleiotropy., Results: When AIT was considered as the outcome, MR evidence suggested an association between Rheumatoid arthritis (RA), Type 1 diabetes (T1D), and Systemic lupus erythematosus (SLE) with AIT. Utilizing the Inverse Variance Weighting (IVW) method, we observed an increased risk of AIT with exposure to RA ( P = 0.024, OR=1.25; 95% CI = 1.03, 1.52), T1D ( P < 0.001, OR=1.27 95% CI = 1.11,1.46), and SLE ( P = 0.037, OR=1.14; 95% CI = 1.04,1.26). Conversely, no significant genetic causal relationship with AIT was found for Sjögren's syndrome (SS), Ankylosing Spondylitis (AS), Multiple sclerosis (MS), Crohn's disease (CD), and Ulcerative colitis (UC)., Conclusion: This study identified RA, T1D, and SLE as triggering factors for AIT. The incidence rate of AIT in patients with RA, T1D, and SLE may be higher than that in the general population. Therefore, individuals with these three diseases should undergo regular monitoring of thyroid-related indicators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Luo and Wang.)

Background: To clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses., Participants: Genetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry., Main Measures: The inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO)., Key Results: AD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism., Conclusion: The findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 You, Duan, Zhou, Yu, Zou, Wei, Chai, Zeng, Xiao, Yuan and Xiao.)

Objective: This study assessed the prevalence of infection, management strategies and associated disease outcomes of COVID-19 among Autoimmune Rheumatic Disease (AIRD) patients in a teaching hospital in Ghana., Design: This was a retrospective cross-sectional study., Setting: Rheumatology Unit, Korle Bu Teaching Hospital., Participants: Autoimmune Rheumatic Disease patients., Results: Thirty-one (31) out of approximately 1700 AIRD patients in the unit tested positive for COVID-19, registering a COVID-19 prevalence of 1.82%. The majority, 25(80.6%), were females with a mean ± SD age of 41.7 ± 12.8 years. Systemic lupus erythematosus was the most affected autoimmune rheumatic condition, reporting fever as the commonest COVID-19-related symptom. Most participants, 22(71%), were managed by the "self-isolation"/home management" strategy. In comparison, 7(22.5%) were monitored at the hospital, with both strategies having resulted in complete recovery. The remaining 2(6.5%) patients who managed under "intensive care unit" strategy resulted in mortality., Conclusion: These findings highlight the relatively low frequency of COVID-19 infection among AIRD patients, the encouraging recovery, and the low severe disease rates observed within this cohort. Additionally, the outcome of self-isolation and home management strategies underscore the importance of personalised approaches to COVID-19 management in this population., Funding: None ., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Objective: Autoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities., Methods: Patients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses., Results: 57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic., Conclusion: In this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic., Competing Interests: Declaration of competing interest Roberta Alexander is a former employee and shareholder of Exagen Inc. May Choi is the Associate Director of MitogenDx. Dr. Sparks has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer, ReCor, Sobi, and UCB unrelated to this work. Dr. Solomon receives salary support through unrelated research contracts to Brigham and Women's Hospital from CorEvitas, Janssen, and Novartis. Dr. Costenbader acknowledges the following: Amgen (Consultant, Grant/Research Support); AstraZeneca (Grant/Research Support); Bristol-Myers Squibb (BMS) (Consultant); Cabaletta Bio (Consultant); Eli Lilly (Consultant); Exagen Inc. (Grant/Research Support); Gilead (Grant/Research Support); GlaxoSmithKline (GSK) (Consultant, Grant/Research Support); Janssen (Consultant, Grant/Research Support). The funders had no role in the decision to publish or preparation of this manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard University, its affiliated academic health care centers, or the National Institutes of Health., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The development of certain immune-mediated diseases (IMD) in patients with inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis (UC)] has been linked to treatment of IBD. Hair loss in some patients may be due to immune-mediated alopecia areata (AA). Risk factors and outcomes of AA in patients with IBD have not been previously explored., Methods: This was a retrospective, multi-center case-control study. Cases were identified as individuals who developed IBD before AA diagnosis. Controls comprised of those who were never diagnosed with AA and treated contemporaneously, selected using random number generator. We extracted demographic and IBD treatment history. Severity of Alopecia Tool (SALT) was used to stratify AA severity. AA outcomes and interventions were compared within controls., Results: We identified 58 cases and 90 controls. Cases had significantly higher rate of tumor necrosis factor α antagonist (anti-TNF) use compared to controls (40.7% vs. 20.0%, p = 0.006). Both groups had similar IBD disease location, behavior, and related surgery. Majority of cases had endoscopic remission or mild disease activity at AA diagnosis. There was no difference in partial or complete improvement of AA between those who stopped or continued IBD therapy (p = 0.57). Those with severe AA were significantly less likely to have complete (0% vs 33.3%, p = 0.01) or any improvement (50% vs 84.9%, p = 0.02) of AA compared to those with non-severe AA., Discussion: Individuals with IBD who later develop AA were more likely to have been on anti-TNF at time of AA onset. Severity of AA was a significant predictor of AA resolution. Fortunately many patients had improvement in their AA despite continuation of IBD therapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aims to conduct an extensive analysis of autoimmune bullous diseases, particularly pemphigus vulgaris and bullous pemphigoid, in Shanghai, China, from 2016 to 2023. It seeks to understand the demographic profiles, comorbidities, mortality rates, risk factors, and socioeconomic impacts associated with autoimmune bullous disease., Methods: A cross-sectional study design was employed, enrolling 1,072 patients. Diagnostic measures included clinical manifestations, histopathology, direct immunofluorescence, and serologic tests. The study also involved a detailed socioeconomic analysis and evaluation of occupational risks., Results: The findings highlight a significant occupational risk in industries requiring enhanced safety measures, with a notable prevalence of autoimmune bullous disease among workers in these sectors. A considerable portion of the patients were from low-income backgrounds with limited literacy, indicating the economic burden of autoimmune bullous disease. A key discovery of the study is the potential pathological link between autoimmune bullous disease and interstitial lung disease., Conclusion: This research, one of the first comprehensive studies on autoimmune bullous disease in China, underscores the need for targeted healthcare strategies and further investigation into autoimmune bullous disease, particularly its relationship with interstitial lung disease., (© 2024. The Author(s).)

Although Janus kinase inhibitor (JAKi) therapy is used for patients with autoimmune diseases (AD), one safety concern, interstitial lung disease (ILD), is life-threatening. We evaluated actual usage of JAKi and safety upon JAKi treatment, in an epidemiological retrospective cohort study utilizing the electronic medical record database in Japan. Among 391,565 AD patients, we analyzed data of new-users receiving JAKi or tumor necrosis factor alpha inhibitor (TNFi)/biologics during the period July 2013-May 2022. ILD (ICD10: J70.2, J70.3, J70.4 and J84) criteria were defined: new-ILD (1) and new-ILD (2) which differed in the latter's prompter therapeutics cessation upon ILD development. We analyzed ILD occurrence and death, ILD cumulative incidence by the Kaplan-Meier method, and hazard ratio (HR) by the Cox model, for 957 JAKi and 3931 TNFi users. JAKi use has become widespread amidst additional drug-development. Among JAKi users, two-year new-ILD (2) incidence, at 1.4%, was higher than for TNFi users (risk ratio: new-ILD (2) 1.75, death 2.31). Cumulative incidence (2.9% in 20.48 days) was also significantly higher (log-rank test p  = .013, HR 2.23 (95% CI 1.16-4.27)); risk factors estimated by HR included JAKi (2.14), rheumatoid arthritis (4.94), diabetes mellitus (2.67) and cerebrovascular disease (2.86). ILD screening is essential.

Background and Aims: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel disease (IBD). However, there is limited overlap between IBD and PSC risk genes, but a stronger association between PSC and other autoimmune conditions. We aimed to assess the coexistence and familial association of autoimmune disorders in PSC, and the influence of autoimmune comorbidity on severe outcomes., Approach and Results: In a matched cohort study, 1378 individuals with PSC and 13,549 general population comparators and their first-degree relatives were evaluated. National registries provided data on diagnoses and outcomes (liver transplantation, hepatobiliary cancer, and liver-related death). The OR of autoimmune disease was estimated by logistic regression. The Fine and Gray competing risk regression estimated HRs for severe outcomes. The prevalence of non-IBD, non-autoimmune hepatitis, and autoimmune disease was 18% in PSC and 11% in comparators, OR: 1.77 (95% CI: 1.53-2.05). Highest odds were seen for celiac disease [OR: 4.36 (95% CI: 2.44-7.49)], sarcoidosis [OR: 2.74 (95% CI: 1.29-5.33)], diabetes type 1 [OR: 2.91 (95% CI: 2.05-4.05)], and autoimmune skin disease [OR: 2.15 (95% CI: 1.52-2.96)]. First-degree relatives of individuals with PSC had higher odds of developing IBD, autoimmune hepatitis, and any autoimmune disease than relatives of the comparators [OR: 3.25 (95% CI: 2.68-3.91); OR: 5.94 (95% CI: 2.82-12.02); OR: 1.34 (95% CI: 1.19-1.50)]. Autoimmune comorbidity in PSC was not associated with poorer outcomes [HR: 0.96 (95% CI: 0.71-1.28)]., Conclusions: Individuals with PSC and their first-degree relatives had higher odds of autoimmune disease compared to matched comparators. This finding provides validation for prior genetic discoveries at a phenotypic level. Autoimmune comorbidity did not impact severe outcomes., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Importance: Alopecia areata (AA) has been associated with multiple comorbidities, yet information regarding the timing of comorbidity development after AA diagnosis is limited., Objective: To evaluate the prevalence and new-onset incidence of psychiatric and autoimmune comorbidities in patients with AA in the US., Design, Setting, and Participants: This retrospective cohort analysis used data collected from January 1, 2007, to April 30, 2023, from the Merative MarketScan Research Databases, which contains medical and drug claims data from more than 46 million patients in the US. Data from adolescent and adult patients (aged 12-64 years) diagnosed with AA and patients without AA (ie, controls) were evaluated. For some analyses, patients with AA were matched (1:4) to controls based on sex, age, and geographic region., Main Outcomes and Measures: Prevalence (at the time of AA diagnosis) and incidence (new onset after AA diagnosis) of psychiatric and autoimmune diseases were reported as percentage of patients. Risk of developing a new-onset psychiatric or autoimmune disease after AA diagnosis was calculated as adjusted hazard ratios (AHRs) with 95% CIs., Results: At baseline, 63 384 patients with AA and 3 309 107 without AA were identified. After matching, there were 16 512 and 66 048 patients in the AA and control groups, respectively, with a mean (SD) age of 36.9 (13.4) years and 50.6% of whom were female. Compared with the unmatched controls, patients with AA had higher prevalence of psychiatric (30.9% vs 26.8%; P < .001) and autoimmune (16.1% vs 8.9%; P < .0001) comorbidities at AA diagnosis; incidence was also higher in patients with AA (without history of these comorbidities) vs the matched control group. Patients with AA vs controls had a significantly higher risk of developing a psychiatric (AHR, 1.3; 95% CI, 1.3-1.4) or autoimmune (AHR, 2.7; 95% CI, 2.5-2.8) comorbidity., Conclusions and Relevance: In this cohort study, patients with AA had a higher prevalence of autoimmune and psychiatric comorbidities at AA diagnosis and demonstrated an elevated risk of new-onset autoimmune and psychiatric comorbidities after their diagnosis. These data highlight the most common comorbidities among patients with AA and may help physicians counsel and monitor patients newly diagnosed with AA.

Competing Interests: Conflicts of interest None disclosed.

Objective: Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases., Methods: Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC., Results: Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004)., Conclusion: In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections., (Copyright © 2024 by the Journal of Rheumatology.)

Objectives: Autoimmune disorders are multifactorial but occupational exposures have long been implicated, including respirable crystalline silica (RCS). A modern epidemic of silicosis is emerging internationally, associated with dry processing of engineered stone with high (>90%) RCS content. We aimed to investigate the prevalence of clinical autoimmune disease and common autoantibodies in exposed workers., Methods: Stone benchtop industry workers in Victoria, Australia were offered free screening for silicosis and related disorders. Symptoms or diagnoses of autoimmune disease were evaluated by questionnaire and blood tests taken for rheumatoid factor (RF), antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs)., Results: Among 1238 workers (93.3% male) screened from 2019 to 2021, 0.9% were confirmed with autoimmune disease. Among those without clinical disease, 24.6% had detectable ANAs (93.5% male), 4.6% detectable ENAs and 2.6% were positive for RF. Silicosis was diagnosed in 253 workers (24.3% of those with diagnostic information available). Of those with ANA readings, 54 (6.6%) had ANA titre >1:320. The likelihood of positive autoantibodies increased with age; smoking; higher exposure to RCS and silicosis diagnosis., Conclusion: The proportion of workers with detectable ANAs or ENAs was considerably higher than the 5%-9% expected in the general population. Some of the antibodies detected (eg, Scl-70, CENPB) have high sensitivity and specificity for systemic sclerosis. Long-term follow-up will be needed to estimate incidence. Rheumatologists should explore occupational history in new cases of autoimmune disease. Screening for autoimmune disease is indicated in workers exposed to RCS as these individuals need specialised management and may be entitled to compensation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori ( H. pylori ) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori . Prospective studies in H. pylori -naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The causality of autoimmune diseases with frailty has not been firmly established. We conducted this Mendelian randomization (MR) study to unveil the causal associations between autoimmune diseases with frailty., Methods: A MR analyses were performed to explore the relationships between autoimmune disease and frailty, using summary genome-wide association statistics., Results: Through a comprehensive and meticulous screening process, we incorporated 46, 7, 12, 20, 5, and 53 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for hypothyroidism, hyperthyroidism, rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS), and overall autoimmune disease, respectively. Our analysis revealed that hypothyroidism (OR = 1.023, 95% CI: 1.008-1.038, p = 0.0015), hyperthyroidism (OR = 1.024, 95% CI: 1.004-1.045, p = 0.0163), RA (OR = 1.031, 95% CI: 1.011-1.052, p = 0.0017), T1D (OR = 1.011, 95% CI: 1.004-1.017, p = 0.0012), and overall autoimmune disease (OR = 1.044, 95% CI: 1.028-1.061, p = 5.32*10^-8) exhibited a positive causal effect on frailty. Conversely, there may be a negative causal association between MS (OR = 0.984, 95% CI: 0.977-0.992, p = 4.87*10^-5) and frailty. Cochran's Q test indicated heterogeneity among IVs derived from hypothyroidism, hyperthyroidism, T1D, and overall autoimmune diseases. The MR-Egger regression analyzes revealed an absence of horizontal pleiotropy in any of the conducted analyses., Conclusion: This study elucidates that hypothyroidism, hyperthyroidism, RA, T1D, and overall autoimmune disease were linked to an elevated risk of frailty. Conversely, MS appears to be associated with a potential decrease in the risk of frailty., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Zhang, Ni, Li, Shao, Wang, Xu, Huang, Zhang and Zhao.)

Background: Pregnancy complications might lead to the development of autoimmune diseases in women. This review aims to summarise studies evaluating the association between pregnancy complications and the development of autoimmune diseases in women., Methods: Medline, CINAHL, and Cochrane databases were searched up to January 2024. Nineteen pregnancy complications and 15 autoimmune conditions were included. Title, abstract, full-text screening, data extraction, and quality assessment were performed by two reviewers independently. Data were synthesised using narrative and quantitative methods. Results were presented using odds ratios (OR), relative risks (RR), incidence rate ratios (IRR), and 95% confidence intervals (CI)., Results: Thirty studies were included. One study reported composite exposure to pregnancy complications had a risk of any autoimmune disease RR 3.20 (2.90-3.51) compared to women without pregnancy complications. Women with hyperemesis gravidarum had a higher risk of developing coeliac disease (n = 1) IRR 1.98 (1.27-2.94), Crohn's disease (n = 1) IRR 1.61 (1.25-2.04), psoriasis (n = 1) IRR 1.33 (1.01-1.71), and rheumatoid arthritis (n = 2) IRR 1.35 (1.09-1.64). Miscarriage associated with subsequent diagnosis of Sjogren syndrome (n = 2) IRR 1.33 (1.06-2.81) and rheumatoid arthritis (n = 4) OR 1.11 (1.04-1.20). Gestational hypertension/preeclampsia was linked with the development of systemic sclerosis (n = 2) IRR 2.60 (1.10-4.60) and T1DM (n = 2) IRR 2.37 (2.09-2.68). Stillbirth associated with composite autoimmune conditions (n = 2) RR 5.82 (95% CI 4.87-6.81) and aIRR 1.25 (1.12-1.40). Postpartum psychosis was associated with autoimmune thyroid disease (n = 1) aIRR2.26 (1.61-2.90)., Conclusions: Women with pregnancy complications subsequently had a higher risk of being diagnosed with autoimmune conditions. Whether this is due to pre-existing undiagnosed health conditions or being causally linked to pregnancy complications is not known., (© 2024. The Author(s).)

Rosacea and autoimmune liver diseases (AILDs) are diseases closely associated with immune system abnormalities. AILDs primarily includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, research on the association between these two conditions is limited. Therefore, this study employed the bidirectional Mendelian randomization (MR) method to investigate potential causal relationships between rosacea and AILDs based on genetic predictions. Summary data related to Rosacea, AIH, PSC, and PBC were obtained from public genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary analytical approach, supplemented by the MR-Egger, weighted mode method, weighted median, and simple mode. A series of sensitivity analyses were also conducted to identify heterogeneity and pleiotropy effects. The MR analysis results indicated a significant increase in the risk of rosacea being associated with PBC (OR = 1.09, 95% CI = 1.02-1.18, P = 0.014), but no such association was found with AIH or PSC. Furthermore, this study did not find a significant impact of rosacea on the risk of AILDs. This study represents the first in-depth exploration of the potential causal relationship between rosacea and AILDs using MR analysis. Thes findings suggest an increased risk of rosacea among PBC patients., (© 2024. The Author(s).)

Background: Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging as one potential mechanism. To begin to understand the role of immune dysfunctions in FND, we assessed the prevalence of several common autoimmune diseases (ADs) in a large cohort of patients with FND and examined the influence of psychiatric comorbidities and biological sex., Methods: Using a large biorepository database (Mass General Brigham Biobank), we obtained demographic and clinical data of a cohort of 643 patients diagnosed with FND between January 2015 and December 2021. The proportion of ADs was calculated overall, by sex and by the presence of psychiatric comorbidities., Results: The overall prevalence of ADs in our sample was 41.9%, with connective tissue and autoimmune endocrine diseases being the most commonly observed ADs. Among patients with FND and ADs, 27.7% had ≥2 ADs and 8% met criteria for multiple autoimmune syndrome. Rates of ADs were significantly higher in subjects with comorbid major depressive disorder and post-traumatic stress disorder (p= 0.02). Women represented the largest proportion of patients with concurrent ADs, both in the overall sample and in the subgroups of interest (p's < 0.05)., Conclusions: This study is unique in providing evidence of an association between FND and ADs. Future studies are needed to investigate the mechanisms underlying this association and to understand whether FND is characterised by distinct dysregulations in immune response., Competing Interests: Competing interests: The authors declare no relevant conflict of interest. BAD is the President-elect of the Functional Neurological Disorder Society., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Autoimmune diseases disproportionately impact women and female-specific aspects of reproduction are thought to play a role. We investigated the time-varying association between pregnancy complications and new-onset autoimmune disease in females during the reproductive and midlife years., Methods: We conducted a population-based cohort study of 1 704 553 singleton births to 1 072 445 females in Ontario, Canada (2002-17) with no pre-existing autoimmune disease. Pregnancy complications were preeclampsia, stillbirth, spontaneous preterm birth and severe small for gestational age (SGA). Royston-Parmar models were used to estimate the time-varying association between pregnancy complications and a composite of 25 autoimmune diseases from date of delivery to date of autoimmune disease diagnosis or censoring at death, loss of health insurance, or 31 March 2021. Models were adjusted for baseline socio-demographics, parity and comorbidities., Results: At 19 years (median = 10.9 years of follow-up), cumulative incidence of autoimmune disease was 3.1% in those with a pregnancy complication and 2.6% in those without complications. Adjusted hazard ratio (AHR) curves as a function of time since birth were generally L-shaped. Universally, risks were most elevated within the first 3 years after birth [at 1 year: preeclampsia AHR 1.22, 95% confidence interval (CI) 1.09-1.36; stillbirth AHR 1.36, 95% CI 0.99-1.85; spontaneous preterm birth AHR 1.30, 95% CI 1.18-1.44; severe SGA AHR 1.14, 95% CI 0.99-1.31] and plateaued but remained elevated thereafter., Conclusions: Prior history of pregnancy complications may be an important female-specific risk factor to consider during clinical assessment of females for possible autoimmune disease to facilitate timely detection and treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)