Journal of autoimmunity最新文献

{"title":"Multiple sclerosis-associated EBNA2 variants influence the response to peginterferon beta-1a therapy","authors":"Caterina Veroni ,&nbsp;Fortunata Carbone ,&nbsp;Daniela Ricci ,&nbsp;Stefania Proietti ,&nbsp;Silvia Romano ,&nbsp;Maria Chiara Buscarinu ,&nbsp;Fabiana Rizzo ,&nbsp;Antonio Marrone ,&nbsp;Teresa Micillo ,&nbsp;Francesco Perna ,&nbsp;Federica Garziano ,&nbsp;Gisella Guerrera ,&nbsp;Paola Valentino ,&nbsp;Chiara Meloni ,&nbsp;Gianmarco Bellucci ,&nbsp;Antonio Bertolotto ,&nbsp;Luca Battistini ,&nbsp;Giovanni Ristori ,&nbsp;Diego Centonze ,&nbsp;Giuseppe Matarese ,&nbsp;Rosella Mechelli","doi":"10.1016/j.jaut.2026.103533","DOIUrl":"10.1016/j.jaut.2026.103533","url":null,"abstract":"<div><h3>Background</h3><div>Strong evidence links Epstein-Barr virus (EBV) infection to Multiple Sclerosis (MS). Peginterferon beta-1a (peg-IFN), currently the most used interferon formulation among first-line treatments in MS, displays immunomodulatory, anti-inflammatory, and antiviral properties and remains also an important therapeutic option in conditions such as pregnancy, lactation and aging patients.</div></div><div><h3>Objectives</h3><div>In this study we evaluated the ability of peg-IFN to restore a homeostatic EBV-host interaction in MS by regulating antiviral and immunometabolic responses.</div></div><div><h3>Methods</h3><div>In people with MS (pwMS), peripheral blood mononuclear cells (PBMCs) were analyzed before (T0) and after six months (T6mos) of peg-IFN administration: IFN-stimulated gene (ISG) levels, EBV DNA load, Epstein-Barr nuclear antigen 2 (EBNA2) allele distribution, and T-lymphocyte phenotyping with glycolytic metabolism were assessed.</div></div><div><h3>Results</h3><div>Peg-IFN increased ISG transcription and glycolysis in CD4⁺ T lymphocytes, and reduced EBV DNA load without altering EBNA2 allele distribution. Notably, ISG expression increase at T6mos in pwMS infected by the non-risk 1.3B EBNA2 allele, correlating with a better long-term response to peg-IFN after 2-years. Lower T-cell glycolytic capacity at T0 predicted higher peg-IFN responsiveness in pwMS carrying the 1.3B allele, suggesting that EBNA2 variants might be predictive of response to peg-IFN.</div></div><div><h3>Conclusion</h3><div>Here, we found that infection with MS-associated EBNA2 variants might be involved in the clinical response to peg-IFN therapy. The predictive model developed, which integrates immunological and viral parameters, may help clinicians in a finer selection of first-line therapies tailored to patient profiles, supporting personalized medicine approaches.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103533"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194754","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":"Evaluation of non-invasive techniques for the diagnosis of pulmonary complications in systemic sclerosis and scleroderma-like overlap syndromes: role of lung ultrasound","authors":"Mattia Perazzi ,&nbsp;Eleonora Croce ,&nbsp;Gabriele Macrì ,&nbsp;Roberta Zaira Pedrazzoli ,&nbsp;Daniele Sola ,&nbsp;Filippo Patrucco ,&nbsp;Alessio Paschè ,&nbsp;Stelvio Tonello ,&nbsp;Daria Apostolo ,&nbsp;Federica Vincenzi ,&nbsp;Nicolò Errica ,&nbsp;Ailìa Giubertoni ,&nbsp;Luca Cumitini ,&nbsp;Laura Campinoti ,&nbsp;Riccardo Erbetta ,&nbsp;Giuseppe Patti ,&nbsp;Mario Pirisi ,&nbsp;Mattia Bellan ,&nbsp;Pier Paolo Sainaghi","doi":"10.1016/j.jaut.2026.103537","DOIUrl":"10.1016/j.jaut.2026.103537","url":null,"abstract":"<div><h3>Background and aim</h3><div>Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading cause of death in Systemic Sclerosis (SSc) and severely affect patients’ quality of life. Early, accurate, and non-invasive diagnostic tools are essential for timely treatment. This study investigates the role of lung ultrasonography (LUS) as a screening method for detecting pulmonary involvement in SSc.</div></div><div><h3>Methods</h3><div>A monocentric cross-sectional study was conducted on 72 patients diagnosed with SSc. Lung ultrasound was performed using a 1–5 MHz convex probe across 14 lung fields. B-lines were quantified using the Total Thoracic Ultrasound Score (TTUS). Echocardiographic data, pulmonary function tests, and visual score on high resolution computed tomography (HRCT) were also collected.</div></div><div><h3>Results</h3><div>TTUS scores showed significant correlation with the presence of ILD and PAH (p = 0.001). TTUS positively correlated with pulmonary arterial pressure, Goh score, visual HRCT score, and inversely correlated with DLCO and 6-min walk test performance. LUS demonstrated good diagnostic performance: fewer than 6 B-lines ruled out PAH with 100% sensitivity (specificity 38.8%; AUC 0.77 [0.64–0.90]). The presence of fewer than 5 B-lines excluded ILD with 100% sensitivity. Conversely, more than 15 B-lines indicated ILD (sensitivity 88.9%; specificity 82.5%; accuracy 91.4%; AUC 0.88 [0.79–0.97]).</div></div><div><h3>Conclusions</h3><div>LUS is a reliable, non-invasive tool for detecting pulmonary involvement in SSc: its high negative predictive value allows it to be adopted as a first-line imaging to rule out PAH and ILD.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103537"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326125","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":"Molecular stratification and transcriptome-guided therapeutics in systemic lupus erythematosus with insufficient treatment response","authors":"Lorenzo Beretta ,&nbsp;Chiu Wai Shirley Chan ,&nbsp;Georgia-Savina Moysidou ,&nbsp;Danae-Mona Nöthling ,&nbsp;Alexandra Ainatzoglou ,&nbsp;Andrea Zoli ,&nbsp;Spyridon Katechis ,&nbsp;Antonis Fanouriakis ,&nbsp;Aline Bozec ,&nbsp;Prodromos Sidiropoulos ,&nbsp;Christina Bergmann ,&nbsp;Dimitrios T. Boumpas ,&nbsp;Georg Schett ,&nbsp;George Bertsias ,&nbsp;Panagiotis Garantziotis","doi":"10.1016/j.jaut.2026.103525","DOIUrl":"10.1016/j.jaut.2026.103525","url":null,"abstract":"<div><div>Insufficient treatment response is common in systemic lupus erythematosus (SLE) and may be associated with progressive organ damage, yet the molecular underpinnings of treatment resistance remain elusive. RNA sequencing was performed in blood samples from 21 SLE patients who failed to achieve Lupus Low Disease Activity State after six months of treatment with cyclophosphamide (n = 9), rituximab (n = 5), or belimumab (n = 7). Molecular endotypes were identified via unsupervised clustering of Functional Analysis of Individual Microarray Expression (FAIME) scores and cluster stability was validated in an independent cohort (n = 23). Endotype-specific druggability was assessed using the L1000CDS² platform. The pathway-based molecular stratification revealed three major endotypes among patients with inadequate treatment response: (i) a T cell-centric cluster characterized by enrichment of PD-1 signaling and DNA damage response pathways along with downregulation of CD28 co-stimulatory signaling, indicative of T cell senescence; (ii) a cytokine-driven cluster defined by elevated IL-6 and IL-17 signaling and reduced IL-2 signaling, suggesting a Th17/Treg imbalance and potential responsiveness to cytokine inhibition or low-dose IL-2 therapy; and (iii) an inflammasome-dominant cluster. A multinomial LASSO regression-derived Molecular Endotype Classification Index (MECI) - validated via 1000-fold bootstrap resampling - demonstrated potential as a surrogate marker for endotype assignment (median AUC-ROC 0.889). Transcriptome reversal analysis suggested that patients of the T cell-dominant endotype may be more responsive to CD19 CAR-T cell therapy. In summary, distinct molecular endotypes underlie insufficient response to therapy in SLE, providing a framework for personalized treatment strategies and improved clinical trial design.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103525"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025553","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":"Perinatal use of targeted synthetic DMARDs and maternal-neonatal outcomes in autoimmune disease: A population-based cohort study","authors":"Vienna Cheng ,&nbsp;Eric C. Sayre ,&nbsp;Neda Amiri ,&nbsp;Jacquelyn J. Cragg ,&nbsp;Mark Harrison ,&nbsp;Laurie Proulx ,&nbsp;Mary A. De Vera","doi":"10.1016/j.jaut.2026.103538","DOIUrl":"10.1016/j.jaut.2026.103538","url":null,"abstract":"<div><h3>Objectives</h3><div>While targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) have advanced autoimmune disease management, the paucity of perinatal safety data limits evidence-based decision-making in pregnancy. We aimed to characterize patterns of tsDMARD utilization and evaluate associations between perinatal tsDMARD exposure and maternal and neonatal outcomes, among females with autoimmune disease.</div></div><div><h3>Methods</h3><div>We used linked population-based administrative health databases from British Columbia, Canada (2002-2022). Our study cohort included females with autoimmune disease (‘mothers’) and ≥1 pregnancy, with tsDMARD-exposed pregnancies matched (on disease type, live birth, etc.) to unexposed pregnancies. We examined 6 maternal (e.g., preeclampsia/eclampsia), 11 fetal/neonatal (e.g., congenital anomaly) and 5 fetal/neonatal-maternal outcomes (e.g., Caesarean delivery) using Fisher's exact test. Pregnancies was the unit of analysis.</div></div><div><h3>Results</h3><div>Among 29,749 mothers with autoimmune disease, 19 pregnancies were exposed to tsDMARDs during the perinatal period. Of these, 7 (36.8%) pregnancies were exposed 1-year preconception, with complete discontinuation by the second trimester. Among maternal outcomes, we observed a non-significant association with gestational diabetes (unadjusted odds ratio [uOR] 0.95, 95% confidence interval [CI] 0.13-7.01, p = 0.96). Among fetal/neonatal outcomes, we observed one significant association with preterm birth (uOR 13.45, 95% CI 2.12-85.21, p = 0.01). Among fetal/neonatal-maternal outcomes, we observed a non-significant association with Caesarean delivery (uOR 2.21, 95% CI 0.46-10.74, p = 0.32).</div></div><div><h3>Conclusions</h3><div>Our study provides timely evidence on the perinatal safety of tsDMARDs and demonstrates how population-based data can be leveraged to address confounding in rare exposures. Studies like ours are critical for future data pooling and synthesis to strengthen the evidence on emerging drugs in pregnancy.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103538"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355025","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":"Vascular effects of achieving low disease activity in axial spondyloarthritis – A 2-year prospective treat-to-target study","authors":"Huan Meng ,&nbsp;Sze-Lok Lau ,&nbsp;Isaac T. Cheng ,&nbsp;Vivien PW. Chan ,&nbsp;Shirley K. Ying ,&nbsp;Jolly M. Lee ,&nbsp;Violet K. Lee ,&nbsp;Kitty Y. Kwok ,&nbsp;Isaac C. Yim ,&nbsp;Jack J. Lee ,&nbsp;Cheuk-Chun Szeto ,&nbsp;Bryan P. Yan ,&nbsp;Alex P. Lee ,&nbsp;Ho So ,&nbsp;Lai-Shan Tam","doi":"10.1016/j.jaut.2026.103534","DOIUrl":"10.1016/j.jaut.2026.103534","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the effect of achieving Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity (LDA) on the progression of subclinical atherosclerosis and arterial stiffness in axial spondyloarthritis (axSpA) patients.</div></div><div><h3>Methods</h3><div>Ninety-nine axSpA patients underwent 2 years of tight-control treatment aiming at ASDAS LDA (&lt;2.1). Carotid intima-media thickness (cIMT) was measured using high-resolution ultrasound. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV) and augmentation index (AIx). The primary outcome was the effect of achieving LDA at 12 months (LDA group) on the progression of subclinical atherosclerosis over 24 months. Secondary outcomes included: (1) arterial stiffness progression between LDA and non-LDA groups; (2) subclinical atherosclerosis and arterial stiffness markers between patients who achieved sustained LDA (sLDA) from 12 to 24 months, and the non-sLDA groups over 24 months.</div></div><div><h3>Results</h3><div>Ninety axSpA patients (mean age: 39 ± 10 years, 81.1% male) were included. At 12 months, 74.4% (n = 67) achieved LDA, while 50.0% (n = 45) attained sLDA at 24 months. Multivariate analysis showed achieving LDA at 12 months reduced carotid plaque progression (OR 0.27, 95% CI 0.08-0.95, <em>P</em> = 0.042), while achieving sLDA was associated with less progression in the total plaque area (RR −1.97, 95% CI −3.83 to −0.12, <em>P</em> = 0.038) over 24 months. The changes in cIMT and arterial stiffness between patents who did or did not achieve LDA/sLDA were similar.</div></div><div><h3>Conclusions</h3><div>Effective suppression of inflammation in axSpA patients achieving LDA may be associated with a reduction in subclinical atherosclerosis progression.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103534"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131739","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":"Immunopathogenic role of the HLA-B∗51:01-specific immunopeptidome in Behçet's disease","authors":"Yeji Lee ,&nbsp;Kyung-Cho Cho ,&nbsp;Byung Kyu Cho ,&nbsp;So Hyun Kim ,&nbsp;Jun Won Park ,&nbsp;Dongjin Shin ,&nbsp;Jong-Il Kim ,&nbsp;Insoo Kang ,&nbsp;Eugene C. Yi ,&nbsp;Eun Bong Lee","doi":"10.1016/j.jaut.2026.103523","DOIUrl":"10.1016/j.jaut.2026.103523","url":null,"abstract":"<div><h3>Objective</h3><div>The immunopeptidome, the collection of peptides bound to human leukocyte antigens (HLAs), plays a key role in initiating immune responses. HLA-B∗51:01 is an allele associated with Behçet's disease (BD). However, the role of the immunopeptidome bound to HLA-B∗51:01 in the pathogenesis of BD remains unclear.</div></div><div><h3>Methods</h3><div>We profiled the HLA-bound immunopeptidome using plasma samples from HLA-B∗51:01-positive BD and healthy controls (HCs). HLA-class I molecules were immunoprecipitated, and liquid chromatography–tandem mass spectrometry was performed to compare HLA-bound peptides between HLA-B∗51:01-positive BD with HCs. Potential HLA-B∗51:01-bound peptides, T cell epitopes, were then selected by the binding prediction software NetMHCpan. The immunogenicity of the selected peptides was investigated through enzyme-linked immunospot, flow cytometry, and dextramer staining.</div></div><div><h3>Results</h3><div>We analyzed the immunopeptidome established from BD using two different methods. First, BD-specific peptides were identified. Among 8008 peptides, 2306 were found only in BD patients. The BD-specific immunopeptidome preferred hydrophobic amino acids at position 2. Exome sequencing confirmed the presence of the identified representative peptides. These peptides, when presented on monocyte-derived dendritic cells from HLA-B∗51:01-positive BD patients, effectively activated T cells, causing them to secrete proinflammatory cytokines and express the degranulation marker CD107a. Additionally, BD-predominant peptides were identified, whose amount was increased in BD than in HC. BD-predominant peptides also activated T cells, leading to the secretion of proinflammatory cytokines.</div></div><div><h3>Conclusion</h3><div>The immunopeptidome presented on HLA-B∗51:01-positive BD is distinct from that of HLA-B∗51:01-positive HCs and can activate T cells and secrete proinflammatory cytokines; this may contribute to the pathogenesis of BD.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103523"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996489","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":"Anti-MDA5 monoclonal antibodies from patients with dermatomyositis – B cell characteristics and differential targeting of the helicase domains","authors":"Eveline Van Gompel ,&nbsp;Marina Galešić ,&nbsp;Nicolas Delaroque ,&nbsp;Karolin Kern ,&nbsp;Ragnhild Stålesen ,&nbsp;Antonella Notarnicola ,&nbsp;Deniz Demirdal ,&nbsp;Monika Hansson ,&nbsp;Annika van Vollenhoven ,&nbsp;Edvard Wigren ,&nbsp;Susanne Gräslund ,&nbsp;Michael Szardenings ,&nbsp;Vivianne Malmström ,&nbsp;Ingrid E. Lundberg ,&nbsp;Begum Horuluoglu ,&nbsp;Caroline Grönwall ,&nbsp;Karine Chemin ,&nbsp;Vijay Joshua","doi":"10.1016/j.jaut.2026.103536","DOIUrl":"10.1016/j.jaut.2026.103536","url":null,"abstract":"<div><h3>Objectives</h3><div>Autoantibodies targeting melanoma differentiation associated protein 5 (MDA5) are strongly associated with dermatomyositis (DM) and may contribute to its pathogenesis. Here we aimed to investigate MDA5⁺ B cells, their phenotype and generate MDA5 monoclonal antibodies to assess their epitope specificity.</div></div><div><h3>Methods</h3><div>MDA5-reactive B cells were captured from peripheral blood of patients with anti-MDA5⁺ DM (n = 3) using an MDA5-fluorescent probe. B cell receptor (BCR) sequences were analysed from single-sorted B cells (n = 240). Selected clones were re-expressed as IgG1 monoclonal antibodies (mAbs, n = 23). Reactivity was assessed using recombinant MDA5 protein constructs, peptide epitope mapping, ELISA, western blot and a commercial line blot assay.</div></div><div><h3>Results</h3><div>Of 240 anti-MDA5⁺ sorted B cells, 23 BCRs were re-expressed as mAbs, two of which showed high reactivity and specificity for MDA5. These antibody sequences originated from one CD19⁺IgD⁻CD27⁻CD38⁺ and one CD19⁺IgD⁻CD27⁺CD38⁺ IgG⁺ B cell with low somatic hypermutation (SHM). Both mAbs had nanomolar apparent affinity and bound to sites within the helicase domains of the MDA5 protein but with distinct epitope recognition. Serology screening confirmed targeting of a linear epitope identified in the mAb studies.</div></div><div><h3>Conclusion</h3><div>Our results show that anti-MDA5⁺ B cells recognize the helicase domains, which are the enzymatically active domains of the protein. These results have implications for understanding the etiopathology of anti-MDA5⁺ DM and development of new antigen-specific therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103536"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258238","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":"What's in a name? – juxtaposing T follicular, peripheral and resident helper cells in B cell-driven autoimmune diseases","authors":"Fabiënne van Puijfelik ,&nbsp;Kirsten L. Kuiper ,&nbsp;Jasper Rip ,&nbsp;Joost Smolders ,&nbsp;Marvin M. van Luijn","doi":"10.1016/j.jaut.2026.103535","DOIUrl":"10.1016/j.jaut.2026.103535","url":null,"abstract":"<div><div>Effective humoral immunity depends on tightly regulated interactions between B cells and CD4⁺ T-helper subsets across lymphoid and peripheral tissues. In autoimmune diseases, these regulatory checkpoints fail, enabling autoreactive B cells to mature, infiltrate tissues and/or produce pathogenic autoantibodies. Three major CD4⁺ helper subsets, T follicular helper (T_FH), T peripheral helper (T_PH), and tissue-resident memory (T_RM) cells, play key roles in shaping these responses. T_FH cells are defined by CXCR5, PD-1 and BCL6 expression and orchestrate germinal centre (GC) reactions in secondary lymphoid organs (SLOs). T_PH cells are part of tertiary lymphoid structures (TLS) and provide potent help to memory and atypical B cells and drive antibody-secreting cell formation within inflamed tissues in autoimmune diseases. CD4⁺ T_RM cells are imprinted by local cues to acquire tissue residency programs characterized by CD69 and CD103. Although not exclusively related to B-cell help, their effector function is key for preventing tissue inflammation, including the onset of organ-specific autoimmune diseases. Notably, CD4⁺ T_RM cells share transcriptional programs with T_PH cells as well as circulating precursor T helper subsets such as Th17.1 cells. Understanding the shared and divergent transcriptional, migratory and functional programs of these helper subsets is essential for defining how tissue contexts stimulate pathogenic rather than protective B-cell responses in autoimmunity.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103535"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113100","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":"Interventional studies targeting the prodromal or preclinical phase of immune-mediated disease to benefit patient outcomes: a scoping review","authors":"Kara Moscovitz ,&nbsp;Daivat Bhavsar ,&nbsp;Helen Tremlett","doi":"10.1016/j.jaut.2026.103526","DOIUrl":"10.1016/j.jaut.2026.103526","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1D) often progress through prodromal or preclinical phases before classical symptom onset. These early stages present opportunity for preventative interventions, but evidence on their efficacy and safety has not been systematically synthesized.</div></div><div><h3>Objective</h3><div>This scoping review evaluated interventional studies targeting the prodromal/preclinical phases of MS, RA, SLE, and T1D, with a focus on efficacy and safety outcomes.</div></div><div><h3>Methods</h3><div>We systematically searched MEDLINE, EMBASE, and Web of Science for interventional studies published between January 2010 to June 2024. Studies assessing any intervention in individuals during the early phases of MS, RA, T1D, or SLE were included.</div></div><div><h3>Results</h3><div>Of 1455 screened studies, 23 met inclusion criteria: 13 for RA, 8 T1D, 2 MS, and none for SLE. For RA, abatacept lowered risk of disease onset in some trials (hazard ratio [HR] range = 0.14–0.61), while methotrexate and rituximab showed modest or subgroup-specific benefit. For T1D, teplizumab delayed clinical onset by over two years (median), preserved β-cell function and lowered risk of progression to T1D (adjusted HR = 0.41; 95% CI 0.22–0.78). For MS, teriflunomide (aHR = 0.28; 95% CI 0.11–0.71) and dimethyl fumarate (aHR = 0.07; 95% CI 0.01–0.45) lowered risk of clinical conversion in persons with radiologically isolated syndrome. Interventions demonstrated expected safety profiles.</div></div><div><h3>Conclusion</h3><div>Interventions targeting preclinical or prodromal phases of immune-mediated diseases can delay clinical onset, particularly in RA, T1D, and MS. Progress will require harmonized preclinical definitions, improved risk stratification, longer follow-up, and dedicated efforts in underrepresented diseases such as SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103526"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025595","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":"Immune cell-derived cytokines synergistically interact to drive synovial fibroblast invasive function and metabolic capacity","authors":"Órla Tynan ,&nbsp;Alyssa Gilmore ,&nbsp;Aenea A.I. Brugman ,&nbsp;Achilleas Floudas ,&nbsp;Conor M. Smith ,&nbsp;Dumitru Anton ,&nbsp;Siobhán Wade ,&nbsp;Carl Orr ,&nbsp;Douglas J. Veale ,&nbsp;Ursula Fearon","doi":"10.1016/j.jaut.2025.103519","DOIUrl":"10.1016/j.jaut.2025.103519","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a chronic autoimmune disease, defined by synovial inflammation and joint destruction. A significant proportion of patients still have sub-optimal/no response to current treatments, with recent synovial scRNA-seq studies highlighting the complexity of the inflamed joint. This study investigates synovial-scRNA-seq predicted IL-1β/TGF-β synergistic regulation of RA synovial-fibroblast (FLS) pathogenic function. Synovial bulk RNA-seq analysis demonstrated increased expression of IL-1β and TGF-β signalling components in healthy controls (HC) versus early RA versus established RA, with synovial scRNA-seq demonstrating enrichment in specific RA-FLS clusters. In RA-FLS, IL-1β/TGF-β synergistically increased baseline glycolysis, ECAR:OCR ratio, proton-efflux rate, %PER glycolysis, compensatory glycolysis, and glycolytic genes (GLUT-1, PKM2, PFKFB3). Synergistic dysregulation of mitochondrial function (biogenesis and DRP1 fission protein) and endoplasmic reticulum (ER) stress responses (ER size, stress genes, chaperone protein (PDI)) were also demonstrated. The altered metabolic profile was paralleled by synergistic induction of pro-inflammatory mediators/chemokines including IL-8, MCP-1, MMP-3, and CXCL5 in RA-FLS. IL-1β and non-canonical TGF-β signalling converge on TAK1 activation. Takinib (TAK1-inhibitor) significantly reduced glycolytic and pro-inflammatory responses of RA-FLS. Importantly, in RA <em>ex vivo</em> synovial explants (reflecting the inflamed joint), Takinib reduced spontaneous release of pro-inflammatory mediators and the process of synovial growth. In conclusion, IL-1β/TGF-β synergistically drive a pathogenic RA-FLS phenotype in RA, blockade of which reduces inflammatory and invasive mechanisms.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103519"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819452","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}