Journal of autoimmunity最新文献

{"title":"Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials","authors":"Virginia Solitano ,&nbsp;Yuhong Yuan ,&nbsp;Siddharth Singh ,&nbsp;Christopher Ma ,&nbsp;Olga Maria Nardone ,&nbsp;Gionata Fiorino ,&nbsp;Maria Laura Acosta Felquer ,&nbsp;Lillian Barra ,&nbsp;Maria-Antonietta D'Agostino ,&nbsp;Janet Pope ,&nbsp;Laurent Peyrin-Biroulet ,&nbsp;Silvio Danese ,&nbsp;Vipul Jairath","doi":"10.1016/j.jaut.2024.103331","DOIUrl":"10.1016/j.jaut.2024.103331","url":null,"abstract":"<div><h3>Objectives</h3><div>Advanced combination treatment (ACT), defined as a combination of at least 2 biologic agents, a biologic agent and an oral small molecule, 2 oral small molecules drug with different mechanisms of action is a proposed strategy to improve outcomes in patients with immune-mediated inflammatory disease (IMID). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ACT with monotherapy in patients with select IMIDs.</div></div><div><h3>Methods</h3><div>Through a systematic literature search, we identified 10 RCTs (n = 1154) comparing ACT with single agent therapy (monotherapy). The primary outcome was induction of clinical remission. Secondary outcomes were adverse events, serious adverse events, infections, and serious infections. We performed random-effects meta-analysis and used GRADE to appraise certainty of evidence.</div></div><div><h3>Results</h3><div>Eight out of 10 trials investigated an anti-TNF-α drug (e.g., etanercept, infliximab, golimumab, certolizumab) combined with another biologic (e.g anti-IL-23, anti-integrin, anti-IL-1) or an oral small molecule. There was no significant difference in the likelihood of achieving clinical remission with ACT vs. monotherapy in patients with rheumatoid arthritis (n = 7 RCTs) (RR, 1.75 [95 % CI 0.60–5.13]; moderate heterogeneity (I² = 33 %)] and systemic lupus erythematosus (n = 1) (RR, 1.20 [0.53–2.72]) (GRADE; low certainty evidence). Patients with rheumatoid arthritis in the ACT arm were more likely to experience adverse events (RR, 1.07 [1.01–1.12]) compared to monotherapy. ACT led to higher rates of induction of clinical remission in patients with IBD (n = 2 RCTs) (RR, 1.68 [1.15–2.46]) with minimal heterogeneity (I² = 15 %) (GRADE; low certainty evidence), and no differences in the likelihood of adverse events (RR 0.92 [0.80–1.05]). There were no differences in the risk of infections or serious infections in patients treated with ACT or monotherapy with rheumatological disease or IBD.</div></div><div><h3>Conclusions</h3><div>ACT did not offer clinical benefit in patients with rheumatological IMIDs and resulted in higher rate adverse events in rheumatoid arthritis. ACT may offer clinical benefit without a clear safety signal in patients with IBD, but further trials are warranted. The variability in ACT regimens across studies limits the generalizability of these findings.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103331"},"PeriodicalIF":7.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592542","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 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":"Unraveling the immunomodulatory impact of hydroxychloroquine on peripheral T cells using single-cell RNA sequencing.","authors":"Huizhong Long, Luis Espinosa, Amr H Sawalha","doi":"10.1016/j.jaut.2024.103324","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103324","url":null,"abstract":"<p><p>Hydroxychloroquine (HCQ) is widely used in the treatment of a variety of autoimmune diseases. However, the mechanisms responsible for the immunomodulatory properties of HCQ in T cells remain unclear. Here we used single-cell RNA-sequencing to examine the effect of HCQ on T cells following in vitro stimulation. HCQ treatment led to a reduction in effector CD4⁺ T cells and upregulation of inhibitory genes including CTLA4 and TNFAIP3 in effector and naive CD4⁺ T cells, respectively. HCQ induced a significant expansion of effector CD8⁺ T cells, and significantly upregulated key cytotoxicity genes including GZMA, GZMB, GZMH, KLRD1, NKG7, and PRF1, as well as IFNG expression. Furthermore, HCQ treatment led to a reduction in the CD38⁺ CD8⁺ T cell subset, which is characterized by defective cytotoxicity and thought to both play a pathogenic role and increase susceptibility to infections in autoimmunity. We analyzed single-cell RNA-sequencing data in effector CD8⁺ T cells from lupus patients with or without HCQ treatment and confirmed upregulation of key cytotoxicity genes in patients receiving HCQ. In conclusion, this work provides additional insights into the immunomodulatory effects of HCQ and indicates that HCQ improves T cell cytotoxicity, which could explain a previously suggested protective effect of HCQ against infections in patients with autoimmune diseases.</p>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"103324"},"PeriodicalIF":7.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466404","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":"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":"Extrapulmonary sarcoidosis.","authors":"Paolo Spagnolo, Vasileios Kouranos, Victoria Singh-Curry, Thomas El Jammal, Misha Rosenbach","doi":"10.1016/j.jaut.2024.103323","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103323","url":null,"abstract":"<p><p>Sarcoidosis is a chronic disease of unknown origin that develops when a genetically susceptible host is exposed to an antigen, leading to an exuberant immune response characterized by granulomatous inflammation. Although lung involvement is almost universal as well as the leading cause of morbidity and mortality, virtually any organ can be affected. In particular, sarcoidosis of the heart, nervous system, and eyes can be devastating, leading to death, debilitation and blindness, and a multidisciplinary approach involving expert specialists is required for prompt diagnosis and appropriate treatment. Sarcoidosis of the skin can be disfiguring, thus posing a substantial psychologic and social impact on the patients. The diagnosis is often straightforward in the presence of compatible clinical manifestations in patients with biopsy-proven sarcoidosis, but is challenging when extrapulmonary signs/symptoms occur in isolation. Corticosteroids remain the first line therapy, with immunosuppressive or biologic agents being reserved to patients failing or experiencing side effects from steroids or developing refractory disease.</p>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":" ","pages":"103323"},"PeriodicalIF":7.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380945","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":"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}