Journal of autoimmunity最新文献

{"title":"Unveiling the role of abnormal copper metabolism in systemic lupus erythematosus","authors":"Zigu Chen,&nbsp;Shaowei Yan,&nbsp;Chuiwen Deng,&nbsp;Weichao Wang,&nbsp;Yunhe Guo,&nbsp;Shenxi Deng,&nbsp;Dawei Lu,&nbsp;Linyi Peng,&nbsp;Wen Zhang,&nbsp;Mengtao Li,&nbsp;Xiaofeng Zeng,&nbsp;Fengchun Zhang,&nbsp;Qian Liu,&nbsp;Guibin Jiang","doi":"10.1016/j.jaut.2026.103614","DOIUrl":"10.1016/j.jaut.2026.103614","url":null,"abstract":"<div><h3>Objective</h3><div>Metabolic dysregulation is increasingly implicated in systemic lupus erythematosus (SLE). Given the crucial role of copper (Cu) in immunity, its specific metabolic alterations in SLE remain poorly understood. By integrating cross-sectional exploratory research, transcriptomic analysis, and murine experiments, this study aims to investigate the phenotypic signatures of aberrant Cu metabolism in SLE, alongside its molecular mechanisms and therapeutic potential.</div></div><div><h3>Methods</h3><div>In blood samples from patients and healthy controls, Cu concentrations and stable isotopic ratios (<em>δ</em>⁶⁵Cu) were measured using inductively coupled plasma mass spectrometry (ICP-MS) and multi-collector ICP-MS, respectively. To explore the mechanisms, molecular alterations were assessed using publicly available blood transcriptomic datasets and Western blotting. The effects of Cu modulation on disease progression were further evaluated in lupus-prone MRL/lpr mice treated with the Cu chelator ammonium tetrathiomolybdate (TTM). Statistical analyses included between-group comparisons, analysis of covariance and multivariable logistic regression for confounder adjustment, association analyses, and gene set enrichment analyses.</div></div><div><h3>Results</h3><div>Autoimmune disease patients (n = 50), particularly SLE patients (n = 21), exhibited distinct Cu metabolic profiles compared to healthy controls (n = 34), with elevated plasma Cu concentration (mean 1.38 [95% CI 1.21–1.56] vs 1.20 [95% CI 1.13–1.28] μg/g; <em>P</em> = 0.058) but decreased <em>δ</em>⁶⁵Cu in both plasma (mean −0.33‰ [95% CI −0.45‰–−0.21‰] vs −0.05‰ [95% CI −0.13‰–0.03‰]; <em>P</em> &lt; 0.0001) and blood cells (mean 0.23‰ [95% CI 0.09‰–0.38‰] vs 0.98‰ [95% CI 0.88‰–1.09‰]; <em>P</em> &lt; 0.0001). Key Cu buffering (albumin, ceruloplasmin) and transport (STEAP4) proteins were dysregulated in SLE. Blood transcriptome analysis of SLE patients (n = 264) and healthy subjects (n = 83) from a public database revealed multiple dysregulated genes in Cu metabolism, which were associated with Cu uptake/efflux and pathways related to mitochondrial respiration and collagen cross-linking. In the MRL/lpr mice, limiting Cu bioavailability via TTM alleviated disease severity, reducing lymphadenopathy and kidney inflammation and fibrosis.</div></div><div><h3>Conclusion</h3><div>We highlighted Cu metabolism abnormalities in SLE, proposing blood cell <em>δ</em>⁶⁵Cu as a potential exploratory biomarker. Aberrant Cu metabolism may contribute to SLE pathology, potentially through mitochondrial and collagen-related pathways, and could be modulated by Cu chelation, suggesting a novel perspective for therapeutic intervention in SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"163 ","pages":"Article 103614"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860410","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":"Multimodal computational framework resolves B cell maturation in autoimmunity and ageing","authors":"Hantao Lou,&nbsp;Meihan Zhang,&nbsp;Bo Zhang,&nbsp;Qianjin Lu,&nbsp;Jianqing Zheng,&nbsp;Xuetao Cao","doi":"10.1016/j.jaut.2026.103609","DOIUrl":"10.1016/j.jaut.2026.103609","url":null,"abstract":"<div><div>Identification of the origin of pathogenic immune cells is crucial for therapeutic interventions and diagnosis but pseudotime methods struggle to trace immune cells accurately. Current trajectory inference methods for B cell development and response in health and disease either ignore or underutilize antigen receptor sequence information, limiting their ability to resolve developmental pathways, particularly for pathogenic populations. Widely used methods such as Monocle 3 reconstruct developmental paths from transcriptomic similarity alone, discarding the features from immune receptors. Dandelion has combined the immune receptor features with transcriptomics but it struggles to simulate the trajectory path of B cells. Here we present ClonoTrace, a computational framework that integrates BCR sequence features with transcriptomic trajectory inference through gated fusion of multimodal embeddings. In fetal B cell development and germinal centre development, ClonoTrace demonstrates closer concordance with the canonical reference ordering than Monocle 3 and Dandelion. Applied to systemic lupus erythematosus, ClonoTrace indicates a memory B cell extrafollicular maturation route alongside the naïve B cell route, accompanied by induction of <em>ZEB2</em> with a concomitant decline of <em>BACH2</em> along the trajectory, as a candidate alternative route to pathogenic double negative 2 B cells (DN2) in systemic lupus erythematosus (SLE) patients. In healthy ageing, ClonoTrace resolved three candidate age-related B cell maturation routes, from naïve, IgM⁺ memory and switched-memory B cells, each passing through a DN2-associated transcriptional state that is ordered before age-associated B cells along the inferred trajectory. ClonoTrace's fate probability algorithm indicated that IgM⁺ memory B cell to ABC transition as the leading candidate age-associated transition, which may be distinct from SLE DN2 maturation. ClonoTrace provides a generalizable framework for receptor-informed trajectory inference, describing candidate developmental routes of pathogenic B cell populations in autoimmunity and ageing.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"163 ","pages":"Article 103609"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850464","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":"Rheumatoid factor is associated with systemic relapse in eosinophilic granulomatosis with polyangiitis","authors":"Luca Iorio,&nbsp;Federica Davanzo,&nbsp;Giulia Lorenzoni,&nbsp;Daniele Gasparini,&nbsp;Eleonora Fiorin,&nbsp;Andrea Doria,&nbsp;Dario Gregori,&nbsp;Roberta Ramonda,&nbsp;Roberto Padoan","doi":"10.1016/j.jaut.2026.103613","DOIUrl":"10.1016/j.jaut.2026.103613","url":null,"abstract":"<div><div>Systemic relapse remains a major cause of morbidity in eosinophilic granulomatosis with polyangiitis (EGPA), but widely available prognostic markers are lacking. We retrospectively assessed 83 EGPA patients with rheumatoid factor (RF) tested at diagnosis. Systemic relapse was defined as new or worsening systemic disease activity and treatment escalation, excluding isolated asthma and rhinosinusitis exacerbations. RF-positive patients (45.8%) had higher C-reactive protein levels, more frequent mononeuritis multiplex, and more frequent systemic relapses (39.5% vs. 2.2%, q = 0.002). In the penalised Cox analysis, RF positivity was associated with shorter time to systemic relapse (HR 10.05, 95% CI 2.43–92.57; p &lt; 0.001) and remained associated after adjustment for MPO-ANCA and treatment intensity. RF positivity may support closer surveillance in EGPA.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"163 ","pages":"Article 103613"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813087","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":"Orelabrutinib for systemic lupus erythematosus: A randomised, double-blind, placebo-controlled study","authors":"Ru Li ,&nbsp;Xue Li ,&nbsp;Xiaoxia Zhu ,&nbsp;Shengyun Liu ,&nbsp;Xiao Zhang ,&nbsp;Changhao Xie ,&nbsp;Zili Fu ,&nbsp;Anbin Huang ,&nbsp;Lingyun Sun ,&nbsp;Dongzhou Liu ,&nbsp;Jinxia Zhao ,&nbsp;Ling Wu ,&nbsp;Zhanguo Li","doi":"10.1016/j.jaut.2026.103578","DOIUrl":"10.1016/j.jaut.2026.103578","url":null,"abstract":"<div><h3>Objectives</h3><div>Orelabrutinib is an oral, highly selective, irreversible inhibitor of Bruton's tyrosine kinase (BTK). Preclinical mechanistic studies have demonstrated its therapeutic potential in systemic lupus erythematosus (SLE).</div></div><div><h3>Methods</h3><div>A multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase Ib/IIa study was conducted in 11 centres in China. Patients diagnosed with SLE were randomised 1:1:1:1 to receive oral orelabrutinib at 50 mg, 80 mg, and 100 mg or placebo once daily for 12 weeks, respectively. This trial is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, NCT04305197.</div></div><div><h3>Results</h3><div>Between July 9, 2020 and September 29, 2021, 60 patients were randomised, with 55 patients who completed 12 weeks of treatment. Adverse events (AEs) were mostly mild or moderate. In all evaluable patients, the SLE Response Index (SRI)-4 rates at week 12 were 50%, 62%, and 64% for orelabrutinib at 50 mg, 80 mg, and 100 mg, respectively, compared with 36% for placebo, indicating dose-dependent improvement. Among patients with baseline SLEDAI-2K &gt; 8, significantly higher SRI-4 responses were noted with orelabrutinib at 50 mg (80%, p = 0·048), 80 mg (83%, p = 0·048), and 100 mg (100%, p = 0·029) compared to placebo (0%). SRI-6 responses at week 12 were 36%, 39%, and 21% for orelabrutinib at 50 mg, 80 mg, and 100 mg, respectively, compared with 7% for placebo. Reduced proteinuria, <em>anti</em>-dsDNA, IgG, and IgM and increased C4 were observed with orelabrutinib treatment.</div></div><div><h3>Conclusions</h3><div>Orelabrutinib was well tolerated and potentially efficacious in patients with SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"161 ","pages":"Article 103578"},"PeriodicalIF":7.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054688","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":"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}