Journal of autoimmunity最新文献

{"title":"The emerging role of BLyS/APRIL in autoimmune diseases: Biological characteristics, functions, and therapeutic potential","authors":"Shi-Zhi Hu ,&nbsp;Zhan-Yuan Yuan ,&nbsp;Xiao-Xun Zhang ,&nbsp;Xiao-Jing Yu ,&nbsp;Hai-Yan Ni ,&nbsp;Sheng-Jia Sun ,&nbsp;Tao Xu ,&nbsp;He-Qin Zhan","doi":"10.1016/j.jaut.2024.103329","DOIUrl":"10.1016/j.jaut.2024.103329","url":null,"abstract":"<div><div>Autoimmune diseases (AIDs) are common diseases in the world. Some cases are difficult to cure and can only delay the progression of the diseases. The B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL) plays an important role in B cell homeostasis, regulation of both innate and adaptive immune responses. After binding to their receptors, BLyS/APRIL primarily affects the survival and development of marginal, transitional, and mature B cells. Of note, elevated BLyS/APRIL is seen in many AIDs, such as systemic lupus erythematosus, rheumatoid arthritis, immunoglobulin A nephropathy, etc. Moreover, there is evidence that blocking these two cytokines can control the number of serum autoantibodies, promote the depletion of B lymphocytes, inhibit the activation of T cells and dendritic lymphocytes, and reduce inflammatory stress. Currently, some clinical studies are underway targeting BLyS/APRIL inhibitors for the treatment of AIDs. However, due to the scattered knowledge on the relationship between BLyS/APRIL and AIDs, it is necessary to sort out the existing data. Therefore, in this review, we describe the basic biological characteristics and functions of BLyS/APRIL in AIDs, summarize the potential clinical applications of related inhibitors, especially monoclonal antibodies and recombinant fusion proteins targeting BLyS/APRIL in AIDs, and also outline promising research directions.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103329"},"PeriodicalIF":7.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the landscape of systemic sclerosis-related autoantibodies through RNA immunoprecipitation coupled with massive parallel sequencing","authors":"Janire Perurena-Prieto ,&nbsp;María Teresa Sanz-Martínez ,&nbsp;Laura Viñas-Giménez ,&nbsp;Claudia Codina-Clavaguera ,&nbsp;Laura Triginer ,&nbsp;Fernando Gordillo-González ,&nbsp;Eduardo Andrés-León ,&nbsp;Laura Batlle-Masó ,&nbsp;Javier Martin ,&nbsp;Albert Selva-O’Callaghan ,&nbsp;Ricardo Pujol ,&nbsp;Neil J. McHugh ,&nbsp;Sarah L. Tansley ,&nbsp;Roger Colobran ,&nbsp;Alfredo Guillen-Del-Castillo ,&nbsp;Carmen Pilar Simeón-Aznar","doi":"10.1016/j.jaut.2024.103328","DOIUrl":"10.1016/j.jaut.2024.103328","url":null,"abstract":"<div><h3>Objectives</h3><div>Systemic sclerosis (SSc)-related autoantibodies are widely used diagnostic and prognostic biomarkers. This study aimed to develop a new assay for detecting anti-ribonucleoprotein autoantibodies in SSc based on RNA immunoprecipitation (RNA IP) coupled with massive parallel sequencing.</div></div><div><h3>Methods</h3><div>Serum samples and clinical data were collected from 307 SSc patients. Among these, 57 samples underwent analysis using a new protocol that combines RNA IP with massive parallel sequencing (RIP-Seq). Filtering strategies and statistical outlier detection methods were applied to select RNA molecules that could represent novel ribonucleoprotein autoantigens associated with SSc.</div></div><div><h3>Results</h3><div>Among the 30,966 different RNA molecules identified by RIP-Seq in 57 SSc patients, 197 were ultimately selected. These included all RNA molecules previously identified by RNA IP, which were found to exhibit high counts almost exclusively in samples positive for the autoantibodies associated to the corresponding RNA molecule, indicating high sensitivity and specificity of the RIP-Seq technique. C/D box snoRNAs were the most abundant RNA type identified. The immunoprecipitation patterns of the detected C/D box snoRNAs varied among patients and could be associated with different clinical phenotypes. In addition, other ribonucleoproteins were identified, which could be potential targets for previously undescribed SSc-related autoantibodies. These include H/ACA box snoRNPs, vault complexes, mitochondrial tRNA synthetases, and 7SK snRNP.</div></div><div><h3>Conclusion</h3><div>A novel RIP-Seq assay has been developed to detect autoantibodies targeting ribonucleoprotein complexes in SSc patients. This method successfully identified RNA molecules associated with ribonucleoproteins known to be targeted by SSc-related autoantibodies, validating both the assay and the analysis strategy. Additionally, this approach uncovered RNA molecules associated with ribonucleoproteins that were not previously identified as targets of SSc patients’ sera, suggesting potential new autoantibody candidates in this disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103328"},"PeriodicalIF":7.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel PDC-E2 epitope in primary biliary cholangitis: Application for engineered Treg therapy","authors":"Ritika Tewari ,&nbsp;Soo Jung Yang ,&nbsp;Ethan D. McClain ,&nbsp;Alex Hu ,&nbsp;Emma Mortensen ,&nbsp;Aleah DeSchmidt ,&nbsp;Janice Chen ,&nbsp;Aravind Kancharla ,&nbsp;Akhilesh K. Singh ,&nbsp;Eddie A. James ,&nbsp;Blaire E. Burman ,&nbsp;Asma Siddique ,&nbsp;David J. Rawlings ,&nbsp;Chandra Patel ,&nbsp;Karen Cerosaletti ,&nbsp;Jane H. Buckner","doi":"10.1016/j.jaut.2024.103327","DOIUrl":"10.1016/j.jaut.2024.103327","url":null,"abstract":"<div><div>Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease, characterized by progressive destruction of small intrahepatic bile ducts and portal inflammation. Treatment options are limited, with reliance on liver transplantation in advanced cases. The adaptive immune response is implicated in disease pathogenesis by the presence of anti-mitochondrial antibodies targeting the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) in 90–95 % of patients and T cells infiltrating the portal tracts. Here, we examined T cell responses to peptides derived from PDC-E2, with a focus on CD4 T cell responses restricted to HLA Class II DRB4∗01:01, an allele found in 62 % of PBC patients, to uncover PDC-E2 epitopes that could be used for engineered regulatory T cell (Treg; EngTreg) therapy. Using an activation-induced marker assay and single cell RNA-sequencing, we found clonal expansion of CD4 T cells reactive to PDC-E2 epitopes among both T conventional (Tconv) and Tregs. Those T cell receptor (TCR) repertoires were non-overlapping and private and included TCRs specific for a novel PDC-E2 epitope restricted to DRB4∗01:01. CD4 Tconv cells reactive to the PDC-E2 novel epitope showed phenotypic heterogeneity skewed towards T follicular helper cells. Using a TCR specific for this novel PDC-E2 epitope, we created an EngTreg that suppressed PDC-E2-specific polyclonal CD4 Tconv cells from PBC patients. This study advances knowledge of PDC-E2-specific T cell responses and introduces a novel PDC-E2 epitope recognized by both Tconv and Tregs. Generation of EngTreg specific for this epitope provides therapeutic potential for PBC.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103327"},"PeriodicalIF":7.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 mRNA vaccines do not worsen autoimmunity in patients with autoimmune liver diseases","authors":"Tobias Kälin ,&nbsp;Katia Passarin ,&nbsp;Magdalena Filipowic-Sinnreich ,&nbsp;David Semela ,&nbsp;Tanja Seifert ,&nbsp;Federica Sallusto ,&nbsp;Diego Vergani ,&nbsp;Andreas Cerny ,&nbsp;Giorgina Mieli-Vergani ,&nbsp;Benedetta Terziroli Beretta-Piccoli ,&nbsp;The Swiss Autoimmune Hepatitis Cohort Study,&nbsp;The Swiss Primary Biliary Cholangitis Cohort Study,&nbsp;The Swiss Primary Sclerosing Cholangitis Study","doi":"10.1016/j.jaut.2024.103325","DOIUrl":"10.1016/j.jaut.2024.103325","url":null,"abstract":"<div><h3>Introduction and aims</h3><div>mRNA vaccines against Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) infection have been associated with immune-related adverse reactions. We aimed at investigating whether SARS-CoV-2 vaccines may worsen autoimmune reactions in patients with autoimmune liver diseases.</div></div><div><h3>Methods</h3><div>We centrally tested a large panel of liver- and non-liver-related autoantibodies in patients with primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and in healthcare workers (HW) before and after SARS-CoV-2 mRNA vaccines.</div></div><div><h3>Results</h3><div>49 PBC, 35 AIH, 9 PSC and 38 HW were included. The proportion of subjects with at least one autoantibody positivization after vaccination was 11 % for HW, 37 % for AIH, 35 % for PBC and 56 % for PSC patients, patients having a significantly higher frequency of positivization as compared to HW. The proportion of seropositive subjects before vaccination who had at least one autoantibody negativization was 25 % for HW, 57 % for AIH, 40 % for PBC and 50 % for PSC, AIH patients having a significantly higher frequency of negativization as compared to HW. In the AIH group, the number of autoantibody negativizations was higher than the number of positivizations. The BNT162b2 vaccine was associated with a higher risk of developing new autoantibodies as compared to the mRNA-1273 vaccine. No new-onset autoimmune disease was observed after one year. One AIH patient had a relapse after vaccination.</div></div><div><h3>Conclusion</h3><div>mRNA SARS-CoV-2 vaccines do not induce short-term worsening of autoimmunity in patients with autoimmune liver diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103325"},"PeriodicalIF":7.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-147-3p in pathogenic CD4 T cells controls chemokine receptor expression for the development of experimental autoimmune diseases","authors":"Norifumi Iijima ,&nbsp;Masaya Yamaguchi ,&nbsp;Tomoya Hayashi ,&nbsp;Yuxiang Rui ,&nbsp;Yuta Ohira ,&nbsp;Yoichi Miyamoto ,&nbsp;Masaaki Niino ,&nbsp;Tatsusada Okuno ,&nbsp;Osamu Suzuki ,&nbsp;Masahiro Oka ,&nbsp;Ken J. Ishii","doi":"10.1016/j.jaut.2024.103319","DOIUrl":"10.1016/j.jaut.2024.103319","url":null,"abstract":"<div><div>Incomplete Freund's adjuvant (IFA) has long been used to trigger autoimmune diseases in animal models, such as experimental autoimmune encephalitis and collagen-induced arthritis. However, the molecular mechanisms that control CD4 T cell effector functions and lead to the development of autoimmune diseases are not well understood. A self-antigen and heat-killed <em>Mycobacterium tuberculosis</em> emulsified in IFA augmented the activation of CD4 T cells, leading to the differentiation of pathogenic CD4 T cells in the draining lymph nodes. In contrast, IFA emulsification did not elicit Foxp3⁺ regulatory T cell expansion. We found that pathogenic Th1 cells expressed miR-147-3p, which targets multiple genes to affect T cell function. Finally, miR-147-3p expressed in CXCR6⁺SLAMF6^– Th1 cells was required for the onset of neurological symptoms through the control of CXCR3 expression. Our findings demonstrate that miR-147-3p expressed in pathogenic CD4 T cells regulates the migratory potential in peripheral tissues and impacts the development of autoimmune diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103319"},"PeriodicalIF":7.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical correlates of lifetime and current comorbidity patterns in autoimmune and inflammatory diseases","authors":"Signe Hässler ,&nbsp;Roberta Lorenzon ,&nbsp;Marie Binvignat ,&nbsp;Claire Ribet ,&nbsp;Alexandra Roux ,&nbsp;Catherine Johanet ,&nbsp;Chloé Amouyal ,&nbsp;Serge Amselem ,&nbsp;Francis Berenbaum ,&nbsp;Olivier Benveniste ,&nbsp;Patrice Cacoub ,&nbsp;Gilles Grateau ,&nbsp;Agnès Hartemann ,&nbsp;David Saadoun ,&nbsp;Joe-Elie Salem ,&nbsp;Jérémie Sellam ,&nbsp;Philippe Seksik ,&nbsp;Eric Vicaut ,&nbsp;Encarnita Mariotti-Ferrandiz ,&nbsp;Michelle Rosenzwajg ,&nbsp;David Klatzmann","doi":"10.1016/j.jaut.2024.103318","DOIUrl":"10.1016/j.jaut.2024.103318","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune and inflammatory diseases (AIDs) are a heterogeneous group of disorders with diverse etiopathogenic mechanisms. This study explores the potential utility of family history, together with present and past comorbidities, in identifying distinct etiopathogenic subgroups. This approach may facilitate more accurate diagnosis, prognosis and personalized therapy.</div></div><div><h3>Methods</h3><div>We performed a multiple correspondence analysis on patients' comorbidities, followed by hierarchical principal component clustering of clinical data from 48 healthy volunteers and 327 patients with at least one of 19 selected AIDs included in the TRANSIMMUNOM cross-sectional study.</div></div><div><h3>Results</h3><div>We identified three distinct clusters characterized by: 1) the absence of comorbidities, 2) polyautoimmunity, and 3) polyinflammation. These clusters were further distinguished by specific comorbidities and biological parameters. Autoantibodies, allergies, and viral infections characterized the polyautoimmunity cluster, while older age, BMI, depression, cancer, hypertension, periodontal disease, and dyslipidemia characterized the polyinflammation cluster. Rheumatoid arthritis patients were distributed across all three clusters. They had higher DAS28 and prevalence of extra-articular manifestations when belonging to the polyinflammation and polyautoimmunity clusters, and also lower ACPA and RF seropositivity and higher pain scores within the polyinflammation cluster. We developed a model allowing to classify AID patients into comorbidity clusters.</div></div><div><h3>Conclusions</h3><div>In this study, we have uncovered three distinct comorbidity profiles among AID patients. These profiles suggest the presence of distinct etiopathogenic mechanisms underlying these subgroups. Validation, longitudinal stability assessment, and exploration of their impact on therapy efficacy are needed for a comprehensive understanding of their potential role in personalized medicine.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103318"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle autoantibodies","authors":"Yan Hua ,&nbsp;Panpan Jiang ,&nbsp;Chunyang Dai ,&nbsp;Ming Li","doi":"10.1016/j.jaut.2024.103322","DOIUrl":"10.1016/j.jaut.2024.103322","url":null,"abstract":"<div><div>Autoantibodies are immunoglobulin proteins produced by autoreactive B cells responding to self-antigens. Extracellular vesicles (EVs) are membranous structures released by almost all types of cells and extensively distributed in various biological fluids. Studies have indicated that EVs loaded with self-antigens not only play important roles in antigen presentation and autoantibody production but can also form functional immune complexes with autoantibodies (termed EV autoantibodies). While numerous papers have summarized the production and function of pathogenic autoantibodies in diseases, especially autoimmune diseases, reviews on EV autoantibodies are rare. In this review, we outline the existing knowledge about EVs, autoantibodies, and EV antigens, highlighting the formation of EV autoantibodies and their functions in autoimmune diseases and cancers. In conclusion, EV autoantibodies may be involved in the occurrence <u>of disease(s)</u> and also serve as potential non-invasive markers that could help in the diagnosis and/or prognosis <u>of disease</u>. Additional studies designed to define in more detail the molecular characteristics of EV autoantibodies and their contribution to disease are recommended.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103322"},"PeriodicalIF":7.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoreactive B cells remain active despite clinical disease control in rheumatoid arthritis","authors":"Sam Neppelenbroek ,&nbsp;Nienke J. Blomberg ,&nbsp;Arieke S.B. Kampstra ,&nbsp;Joost G.K. van der Hem ,&nbsp;Tom W.J. Huizinga ,&nbsp;René E.M. Toes ,&nbsp;Hans U. Scherer","doi":"10.1016/j.jaut.2024.103320","DOIUrl":"10.1016/j.jaut.2024.103320","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune diseases (AIDs) are frequently hallmarked by the presence of autoreactive B cell responses which are involved in disease pathogenesis. However, the dynamics of such responses and their relation to clinical disease activity in humans is poorly understood. Rheumatoid arthritis (RA), a prototypic chronic AID, is hallmarked by B cell responses directed against citrullinated proteins.</div></div><div><h3>Objective</h3><div>To determine the relation between the activity of the anti-citrullinated protein antibody (ACPA) B cell response and clinical disease activity in ACPA⁺ patients with RA.</div></div><div><h3>Methods</h3><div>Expression of B cell activation markers by ACPA⁺, tetanus toxoid (TT)⁺ and ACPA⁻ memory B cells (MBCs) from peripheral blood of ACPA⁺ RA patients receiving different treatments was analyzed by flow cytometry. Results were correlated to clinical disease activity.</div></div><div><h3>Results</h3><div>Compared to TT⁺ and ACPA⁻ MBCs, ACPA⁺ MBCs displayed a highly activated phenotype as evidenced by increased expression of Ki-67, CD86, CD80, CD19 and CD20 and reduced expression of CD32. The activated phenotype of ACPA⁺ MBCs did not associate with clinical disease activity in a cross-sectional analysis of RA patients treated with various therapeutic agents. Also, in a longitudinal analysis of patients treated with Janus kinase (JAK) inhibitors, ACPA⁺ MBCs retained their activated phenotype despite effective control of inflammation and clinical disease.</div></div><div><h3>Conclusion</h3><div>ACPA⁺ MBCs remain active despite clinical disease control in patients with RA across a range of interventions. This persistent activity indicates the absence of immunological remission and might explain why ACPA⁺ patients rarely reach sustained drug-free remission and frequently flare upon drug tapering.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103320"},"PeriodicalIF":7.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The risk of cancer in pediatric-onset immune-mediated inflammatory diseases – A nationwide study","authors":"Andrea Ehrström ,&nbsp;Sabine Jansson ,&nbsp;Marianne Hørby Jørgensen ,&nbsp;Vibeke Wewer ,&nbsp;Mikkel Malham","doi":"10.1016/j.jaut.2024.103321","DOIUrl":"10.1016/j.jaut.2024.103321","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Adult-onset immune-mediated inflammatory disease (IMID) increases the risk of several cancers. However, data on pediatric-onset IMID (pIMID) remains scarce. We estimated the long-term cancer risk in pIMID and the association between medical treatment and specific cancers.</div></div><div><h3>Methods</h3><div>We used the nationwide Danish health registers to identify pIMID patients diagnosed from Jan 1, 1980 to Dec 31, 2018. Patients were matched with ten reference individuals based on age, sex, and residence. The primary exposure was pIMID, including autoimmune hepatitis, primary sclerosing cholangitis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, systemic lupus erythematosus, vasculitis, and connective tissue disease. Secondary exposures were immunomodulators and tumor necrosis factor-α antagonists (anti-TNFα). The primary outcome was cancer. Estimates are presented as hazard ratios adjusted for family income at diagnosis (AHR).</div></div><div><h3>Results</h3><div>We included 12,664 pIMID patients and 109,274 reference individuals. Median follow-up time was 10.6 (interquartile range: 5.4–17.7) years for patients and 10.2 (interquartile range: 5.2–17.3) years for reference individuals. Patients with pIMID had a twofold higher cancer risk (AHR 2.2 [95 % confidence interval (CI): 1.8–2.6]) compared with reference individuals. Thiopurine treatment was associated with a higher risk of lymphoma (AHR 6.1 [95%CI: 2.2–16.8]) and skin cancer (AHR 6.1 [95%CI: 2.4–15.4]). Anti-TNFα treatment was associated with a higher risk of lymphoma (AHR 4.9 [95%CI: 1.1–22.6]).</div></div><div><h3>Conclusions</h3><div>We found an increased cancer risk in patients with pIMID followed into adulthood. Additionally, thiopurines and anti-TNFα were associated with increased lymphoma and skin cancer risks. This highlights the importance of individualized immunotherapy and cancer surveillance.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103321"},"PeriodicalIF":7.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise, autoimmune diseases and T-regulatory cells","authors":"Miri Blank ,&nbsp;Daphna Israeli ,&nbsp;Yehuda Shoenfeld","doi":"10.1016/j.jaut.2024.103317","DOIUrl":"10.1016/j.jaut.2024.103317","url":null,"abstract":"<div><p>Diverse forms of physical activities contribute to improvement of autoimmune diseases and may prevent disease burst. T regulatory cells (Tregs) maintain tolerance in autoimmune condition. Physical activity is one of the key factors causing enhancement of Tregs number and functions, keeping homeostatic state by its secrotome. Muscles secrete myokines like IL-6, PGC1α (PPARγ coactivator-1 α), myostatin, transforming growth factor β (TGF-β) superfamily), IL-15, brain derived neurotrophic factor (BDNF) and others. The current concept points to the role of exercise in induction of highly functional and stable muscle Treg phenotype. The residing-Tregs require IL6Rα signaling to control muscle function and regeneration. Skeletal muscle Tregs IL-6Rα is a key target for muscle-Tregs cross-talk. Thus, interplay between the Tregs-skeletal muscle, following exercise, contribute to the balance of immune tolerance and autoimmunity. The cargo delivery, in the local environment and periphery, is performed by extracellular vesicles (EVs) secreted by muscle and Tregs, which deliver proteins, lipids and miRNA during persistent exercise protocols. It has been suggested that this ensemble induce protection against autoimmune diseases.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103317"},"PeriodicalIF":7.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}