Tobias Kälin , Katia Passarin , Magdalena Filipowic-Sinnreich , David Semela , Tanja Seifert , Federica Sallusto , Diego Vergani , Andreas Cerny , Giorgina Mieli-Vergani , Benedetta Terziroli Beretta-Piccoli , The Swiss Autoimmune Hepatitis Cohort Study, The Swiss Primary Biliary Cholangitis Cohort Study, The Swiss Primary Sclerosing Cholangitis Study
{"title":"SARS-CoV-2 mRNA vaccines do not worsen autoimmunity in patients with autoimmune liver diseases","authors":"Tobias Kälin , Katia Passarin , Magdalena Filipowic-Sinnreich , David Semela , Tanja Seifert , Federica Sallusto , Diego Vergani , Andreas Cerny , Giorgina Mieli-Vergani , Benedetta Terziroli Beretta-Piccoli , The Swiss Autoimmune Hepatitis Cohort Study, The Swiss Primary Biliary Cholangitis Cohort Study, 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}
Norifumi Iijima , Masaya Yamaguchi , Tomoya Hayashi , Yuxiang Rui , Yuta Ohira , Yoichi Miyamoto , Masaaki Niino , Tatsusada Okuno , Osamu Suzuki , Masahiro Oka , Ken J. Ishii
{"title":"miR-147-3p in pathogenic CD4 T cells controls chemokine receptor expression for the development of experimental autoimmune diseases","authors":"Norifumi Iijima , Masaya Yamaguchi , Tomoya Hayashi , Yuxiang Rui , Yuta Ohira , Yoichi Miyamoto , Masaaki Niino , Tatsusada Okuno , Osamu Suzuki , Masahiro Oka , 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<sup>+</sup> 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<sup>+</sup>SLAMF6<sup>–</sup> 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}
Signe Hässler , Roberta Lorenzon , Marie Binvignat , Claire Ribet , Alexandra Roux , Catherine Johanet , Chloé Amouyal , Serge Amselem , Francis Berenbaum , Olivier Benveniste , Patrice Cacoub , Gilles Grateau , Agnès Hartemann , David Saadoun , Joe-Elie Salem , Jérémie Sellam , Philippe Seksik , Eric Vicaut , Encarnita Mariotti-Ferrandiz , Michelle Rosenzwajg , David Klatzmann
{"title":"Clinical correlates of lifetime and current comorbidity patterns in autoimmune and inflammatory diseases","authors":"Signe Hässler , Roberta Lorenzon , Marie Binvignat , Claire Ribet , Alexandra Roux , Catherine Johanet , Chloé Amouyal , Serge Amselem , Francis Berenbaum , Olivier Benveniste , Patrice Cacoub , Gilles Grateau , Agnès Hartemann , David Saadoun , Joe-Elie Salem , Jérémie Sellam , Philippe Seksik , Eric Vicaut , Encarnita Mariotti-Ferrandiz , Michelle Rosenzwajg , 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 , Panpan Jiang , Chunyang Dai , 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}
Sam Neppelenbroek , Nienke J. Blomberg , Arieke S.B. Kampstra , Joost G.K. van der Hem , Tom W.J. Huizinga , René E.M. Toes , Hans U. Scherer
{"title":"Autoreactive B cells remain active despite clinical disease control in rheumatoid arthritis","authors":"Sam Neppelenbroek , Nienke J. Blomberg , Arieke S.B. Kampstra , Joost G.K. van der Hem , Tom W.J. Huizinga , René E.M. Toes , 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<sup>+</sup> patients with RA.</div></div><div><h3>Methods</h3><div>Expression of B cell activation markers by ACPA<sup>+</sup>, tetanus toxoid (TT)<sup>+</sup> and ACPA<sup>−</sup> memory B cells (MBCs) from peripheral blood of ACPA<sup>+</sup> 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<sup>+</sup> and ACPA<sup>−</sup> MBCs, ACPA<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> MBCs retained their activated phenotype despite effective control of inflammation and clinical disease.</div></div><div><h3>Conclusion</h3><div>ACPA<sup>+</sup> 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<sup>+</sup> 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 , Sabine Jansson , Marianne Hørby Jørgensen , Vibeke Wewer , 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 , Daphna Israeli , 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}
Xueting Peng , Sijia Wang , Kunyi Wu , Christopher Cook , Liang Li , Zhao Wang , Hanjiang Gu , Mei Lu , Guanglei Hu , Kaixuan Ren , Gang Hu , Weihui Zeng , Yumin Xia , Yale Liu
{"title":"Effect of opioid receptor antagonist on mitigating tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-induced apoptolysis in pemphigus pathogenesis","authors":"Xueting Peng , Sijia Wang , Kunyi Wu , Christopher Cook , Liang Li , Zhao Wang , Hanjiang Gu , Mei Lu , Guanglei Hu , Kaixuan Ren , Gang Hu , Weihui Zeng , Yumin Xia , Yale Liu","doi":"10.1016/j.jaut.2024.103307","DOIUrl":"10.1016/j.jaut.2024.103307","url":null,"abstract":"<div><p>Pemphigus is a severe autoimmune blistering disease characterized by acantholysis triggered by autoantibodies against desmoglein 1 and 3 (DSG1/3). Apoptosis plays a pivotal role in facilitating acantholysis, yet the precise underlying mechanism remains obscure. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to promote apoptosis and disrupt cell junctions, although its involvement in pemphigus pathogenesis remains ambiguous. Our study observed decreased DSG1/3 expression alongside increased TWEAK/fibroblast growth factor-inducible 14 (Fn14) expression and keratinocyte apoptosis in both lesional and perilesional skin. <em>In vitro</em> experiments revealed that TWEAK-stimulated keratinocytes exhibited enhanced apoptosis, STAT1 phosphorylation, and reduced intercellular DSG1/3 expression. Notably, bulk-RNA sequencing unveiled that <em>CASPASE-3</em> was responsible for mediating the DSG1/3 depletion, as confirmed by direct interaction with DSG1/3 in a co-immunoprecipitation assay. Naloxone, known for preserving cellular adhesion and preventing cell death, effectively reduced apoptosis and restored DSG1/3 levels in TWEAK-stimulated keratinocytes. The anti-apoptotic properties of naloxone were further validated in a murine pemphigus model. Our findings elucidate that TWEAK facilitates keratinocyte apoptosis by augmenting caspase-3 activity, leading to DSG1/3 depletion and apoptosis in pemphigus. Importantly, naloxone can counter TWEAK-induced apoptosis in pemphigus pathogenesis, offering a potential therapeutic intervention.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103307"},"PeriodicalIF":7.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124001410/pdfft?md5=bfbe7acfeadea7ac3cd977824b611ea2&pid=1-s2.0-S0896841124001410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229869","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}
Shasha Xie , Ding Bao , Yizhi Xiao , Hongdong Li , Muyao Guo , Bingying Dai , Sijia Liu , Jing Huang , Muyuan Li , Liqing Ding , Qiming Meng , Chun-Liu Lv , Jörg H.W. Distler , Hui Luo , Honglin Zhu
{"title":"Alternative splicing and intron retention: Their profiles and roles in cutaneous fibrosis of systemic sclerosis","authors":"Shasha Xie , Ding Bao , Yizhi Xiao , Hongdong Li , Muyao Guo , Bingying Dai , Sijia Liu , Jing Huang , Muyuan Li , Liqing Ding , Qiming Meng , Chun-Liu Lv , Jörg H.W. Distler , Hui Luo , Honglin Zhu","doi":"10.1016/j.jaut.2024.103306","DOIUrl":"10.1016/j.jaut.2024.103306","url":null,"abstract":"<div><h3>Background</h3><p>Alternative splicing (AS) and intron retention (IR) implicated in multiple pathophysiological processes, have rarely been reported in systemic sclerosis (SSc).</p></div><div><h3>Methods</h3><p>We integrated bulk RNA-seq and 4D label-free mass spectrometry to perform a multi-omics analysis of AS and IR in SSc skin tissue and fibroblasts. RMATS and iREAD were used to identify AS and IR, which were validated by real-time PCR. Spearman correlation and the LASSO method were employed to assess correlations among clinical features, introns, splicing factors (regulators of AS) and proteins.</p></div><div><h3>Findings</h3><p>AS profiles showed distinct alterations in SSc skin tissue, with the most pronounced changes occurring in IR. AS and IR were associated with total modified Rodnan skin score (mRSS) and local skin score. Upon TGF-β stimulation, fibroblasts exhibited significant alterations in IR profiles, affecting genes related to fibroblast proliferation and collagen fibril organization. A comprehensive integrated analysis of introns, exons, and proteome profiles revealed that IR exerted a negative impact on protein expression, with certain changes being under intronic control. RT-PCR confirmed the presence of intron and exon-derived sequences of <em>CTTN, OGA, MED16</em> and <em>PHYKPL</em>. Additionally, notable changes were observed in the regulatory network of splicing factors in SSc skin tissues. These factors are also involved in fibrosis pathways and correlated with clinical features.</p></div><div><h3>Conclusion</h3><p>Totally, abnormal AS, IR profiles and splicing factors were identified in SSc, altered IRs and splicing factors participated in fibrosis-related pathways. IR exerted a negative impact on protein expression in TGF-β-stimulated fibroblasts. Clarification of the IR mechanisms will provide new insights into the pathophysiology of SSc.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103306"},"PeriodicalIF":7.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168031","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":"Therapeutic potentials of adoptive cell therapy in immune-mediated neuropathy","authors":"Siqi Shang , Chongbo Zhao , Jie Lin","doi":"10.1016/j.jaut.2024.103305","DOIUrl":"10.1016/j.jaut.2024.103305","url":null,"abstract":"<div><p>Immune-mediated neuropathy (IMN) is a group of heterogenous neuropathies caused by intricate autoimmune responses. For now, known mechanisms of different IMN subtypes involve the production of autoantibodies, complement activation, enhanced inflammation and subsequent axonal/demyelinating nerve damages. Recent therapeutic studies mainly focus on specific antibodies and small molecule inhibitors previously approved in rheumatoid diseases. Initial strategies based on the pathophysiologic features of IMN should be explored. Adoptive cell therapy (ACT) refers to the emerging immunotherapies in which circulating immunocytes are collected from peripheral blood and modified with killing and immunomodulatory capacities. It consists of chimeric antigen receptor-T cell therapy, T cell receptor-engineered T cell, CAR-Natural killer cell therapy, and others. In the last decade, ACT has demonstrated extraordinary potentials in treating cancers, infectious diseases and autoimmune diseases. Versatile combinations of targets, chimeric domains and effector cells greatly empower ACT to treat complicated immune disorders. In this review, we summarized the advances of ACT and envisioned suitable strategies for different IMN subtypes.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103305"},"PeriodicalIF":7.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168030","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}