Journal of autoimmunity最新文献

{"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":"2025-12-22","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}

{"title":"Proinflammatory CD20+CD3+ T cells as a potential driver of macrophage reprogramming in rheumatoid arthritis","authors":"Suna Jiang ,&nbsp;Jiawei Xue ,&nbsp;Haonan Jia ,&nbsp;Maolin Chu ,&nbsp;Yeye Ma ,&nbsp;Haihong Zhang ,&nbsp;Wenjing Li ,&nbsp;Changju Li ,&nbsp;Yanli Wang ,&nbsp;Hongying Li ,&nbsp;Juan Zhang","doi":"10.1016/j.jaut.2025.103515","DOIUrl":"10.1016/j.jaut.2025.103515","url":null,"abstract":"<div><h3>Objective</h3><div>CD20⁺CD3⁺ T cells, a distinct immune cell population implicated in immune responses, contribute to the development of multiple diseases. However, their role in RA progression, particularly their potential to drive the reprogramming of monocyte-derived macrophages toward a pathogenic state akin to synovial tissue macrophages (STMs), remains unclear.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing and flow cytometry were conducted on RA patients and healthy controls. CD14⁺ monocytes isolated from the peripheral blood of RA patients were co-cultured with CD20⁺CD3⁺ T cells to study their effect on monocyte differentiation. A collagen-induced arthritis (CIA) model was used to assess the pathogenic potential of transferring CD20⁺CD3⁺ T cells.</div></div><div><h3>Results</h3><div>RA patients have a higher frequency of CD20⁺CD3⁺ T cells than healthy controls, with single-cell analysis showing increased ANXA1-FPR1 interaction between these T cells and monocytes. ANXA1⁺CD20⁺CD3⁺ T cells and FPR1⁺ monocytes are more prevalent in RA patients. The role of ANXA1-FPR1 signaling is supported by a higher number of CD48⁺ cells in the MerTK‾CD206‾ macrophages subset after co-culture with CD20⁺CD3⁺ T cells. CIA mice administered CD20⁺CD3⁺ T cells exhibited more severe arthritis and more proinflammatory STMs infiltration than CIA controls.</div></div><div><h3>Conclusions</h3><div>CD20⁺CD3⁺ T cells exacerbate synovitis and drive RA progression by promoting the recruitment and pro-inflammatory differentiation of monocyte-derived macrophages (particularly the CD48⁺MerTK‾CD206‾ subset) via ANXA1-FPR1 signaling, representing a potential therapeutic target.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103515"},"PeriodicalIF":7.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781384","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":"Circadian clock genes: Potential therapeutic targets for autoimmune diseases","authors":"Tian Tian ,&nbsp;Lulu Rao ,&nbsp;Mengzhu Wei ,&nbsp;Jia Du ,&nbsp;Yiyue Gu ,&nbsp;Xiaoyan Wu ,&nbsp;Yang Ma","doi":"10.1016/j.jaut.2025.103516","DOIUrl":"10.1016/j.jaut.2025.103516","url":null,"abstract":"<div><div>Circadian rhythms are endogenous 24-h oscillations in physiological processes, with their regulation dependent on a molecular network comprising the core clock genes (<em>CLOCK, BMAL1, PER, CRY</em>) and other key clock genes (<em>NR1D1/2, RORs</em>). Research indicates that circadian rhythm disruption is a significant risk factor for immune dysregulation, while maintaining circadian rhythm balance may offer new therapeutic avenues for autoimmune diseases. This review systematically examines the regulatory mechanisms of the circadian clock genes in innate immunity, adaptive immunity (particularly Th17 cell differentiation and function), and inflammatory responses. By elucidating their molecular interactions, it clarifies the pivotal role of these clock genes in autoimmune diseases. Additionally, we have summarized research progress on small molecule modulators targeting clock genes, as well as non-pharmacological interventions such as sleep regulation, intermittent fasting (IF)/time-restricted feeding (TRF), and melatonin supplementation.In summary, this review aims to elucidate the role of clock genes in immune regulation and inflammatory responses, emphasizing their potential as therapeutic targets for autoimmune diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103516"},"PeriodicalIF":7.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781365","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":"Humoral correlates of clinical response to thymectomy in myasthenia gravis","authors":"Carla D.F. Sousa ,&nbsp;Paula Terroba-Navajas ,&nbsp;John Tzartos ,&nbsp;Ivana D. Orešković ,&nbsp;Maja Pučić-Baković ,&nbsp;Gordan Lauc ,&nbsp;Yannic C. Bartsch ,&nbsp;Henry J. Kaminski ,&nbsp;Jan D. Lünemann","doi":"10.1016/j.jaut.2025.103517","DOIUrl":"10.1016/j.jaut.2025.103517","url":null,"abstract":"<div><div>Mechanisms by which thymectomy confers its clinical benefit in patients with AChR-antibody (Ab) positive myasthenia gravis (MG) remain poorly understood. We used a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to identify Ab-features that track with clinical response to thymectomy in 78 patients with AChR-Ab positive MG, recruited during the MGTX trial, an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone. Clinically meaningful improvement was defined as a change of at least 3 points on the quantitative MG scale at month 36 compared to baseline. AChR-specific immunoglobulin G (IgG) titers decreased in patients experiencing clinical improvement but remained stable in patients with poor response to therapy. Thymectomized patients showed an accelerated decline in AChR-specific IgG titers. At month 36, the frequency of digalactosylated and monosialylated total IgG Fc-glycans was increased in thymectomized responders compared to non-responders. Fc-glycosylation profiles were unchanged in prednisone only treated patients with or without clinically meaningful improvement. Clinical benefit achieved by thymectomy is strongly associated with an anti-inflammatory IgG Fc-glycosylation profile.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103517"},"PeriodicalIF":7.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781379","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":"Physical work demands and risk of rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus. A Danish longitudinal cohort study","authors":"Helena Breth Nielsen ,&nbsp;Nidhi Gupta ,&nbsp;Astrid Juhl Andersen ,&nbsp;Lene Wohlfahrt Dreyer ,&nbsp;Esben Meulengracht Flachs ,&nbsp;Ida E.H. Madsen ,&nbsp;Henrik Albert Kolstad ,&nbsp;Hans Kromhout ,&nbsp;Camilla Sandal Sejbaek ,&nbsp;Karin Sørig Hougaard","doi":"10.1016/j.jaut.2025.103514","DOIUrl":"10.1016/j.jaut.2025.103514","url":null,"abstract":"<div><h3>Objectives</h3><div>This study assesses the association between physical work demands and rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE) among men and women.</div></div><div><h3>Methods</h3><div>This nationwide, register-based study included more than 1.0 million women and 1.1 million men with employment born between 1960 and 1999 from the Danish Occupational Cohort with eXposure data (DOC∗X). Information on physical work demands was obtained from a job exposure matrix (JEM) and measured as recent physical work demands, accumulated physical work demands, and years with high physical work demands since workforce entry. The populations were followed from 1997 to 2018. Poisson regression models were used to estimate the IRRs for developing RA, SSc, and SLE, identified in the Danish National Patient Registry.</div></div><div><h3>Results</h3><div>Men in occupations with high recent physical work demands (4th quartile vs. 1st quartile: 1.36, 95 % CI 1.31–1.42), higher accumulated physical work demands, and more years with high physical work demands, had a higher risk of diagnosis of RA, while this was not the case for women. Accumulated physical work demands and more years with high physical work demands were associated with a small increased risk of diagnosis of SSc and SLE among men. In women, high physical work demands were associated with a reduced risk of diagnosis of SLE, while the results on SSc were inconsistent.</div></div><div><h3>Conclusion</h3><div>These findings support an association between higher physical work demands and diagnosis of RA and possibly, albeit to a lesser extent, SLE and SSc in men, but not in women.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103514"},"PeriodicalIF":7.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734026","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":"Vasculopathy and vasculitis associated with levamisole-adulterated cocaine: a systematic review","authors":"Martin Scoglio ,&nbsp;Corinne Orlando ,&nbsp;Gregorio P. Milani ,&nbsp;Mario G. Bianchetti ,&nbsp;Gabriel Bronz ,&nbsp;Mattia Rizzi ,&nbsp;Sebastiano A.G. Lava ,&nbsp;Benedetta Terziroli Beretta-Piccoli ,&nbsp;Helmut Beltraminelli ,&nbsp;Marcel M. Bergmann","doi":"10.1016/j.jaut.2025.103505","DOIUrl":"10.1016/j.jaut.2025.103505","url":null,"abstract":"<div><h3>Objective</h3><div>Levamisole, once used as anthelminthic or immunomodulator, is now a common cocaine adulterant. It is linked to a systemic vasculopathy/vasculitis. Our purpose was to review its clinical, serological, and histopathological features.</div></div><div><h3>Methods</h3><div>We conducted a registered systematic review (CRD42024558898) across three databases, without language or date restrictions. Reports documenting a vasculopathy/vasculitis temporally associated with levamisole — either prescribed or as a cocaine adulterant — were included.</div></div><div><h3>Results</h3><div>172 reports describing 302 patients were included. Most cases (N = 282; 93 %) involved cocaine adulterated with levamisole. The skin was involved in 274 (91 %) and the kidney in 64 (21 %) cases. Purpura (228; 83 %) and necrosis (141; 51 %) were the most common skin lesions, predominantly affecting ears and extremities. Among 186 classifiable skin biopsies, a thrombotic vasculopathy was detected in 65, a leukocytoclastic vasculitis in 52, and both a thrombotic vasculopathy and a vasculitis in 70 cases. Among 37 renal biopsies, a pauci-immune crescentic glomerulonephritis and a membranous nephropathy were the most detected features. Leukopenia occurred in 100 (33 %) cases. Among tested cases, anti-neutrophil cytoplasmic antibodies were detected in about 89 % of cases, mostly with a perinuclear (71 %) or an atypical (25 %) pattern. Antibodies targeting the myeloperoxidase were detected in 73 % of the cases. In patients receiving levamisole for therapeutic purposes, the vasculopathy resolved after levamisole withdrawal. A relapse of the vasculopathy was observed after re-exposed to levamisole.</div></div><div><h3>Conclusions</h3><div>Levamisole-induced vasculopathy/vasculitis is a distinctive skin-predominant condition with characteristic clinical and serological features. Withdrawal of levamisole is the cornerstone of management.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103505"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661384","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":"Striatin-3 is a human autoantigen but it is not associated with the S-phase G2 nuclear antigen (SG2NA) staining pattern","authors":"Marvin J. Fritzler ,&nbsp;Yoshinao Muro ,&nbsp;Werner Klotz ,&nbsp;Manfred Herold ,&nbsp;Luis E.C. Andrade ,&nbsp;Marcelle Grecco ,&nbsp;Minoru Satoh ,&nbsp;May Y. Choi ,&nbsp;Maria Infantino ,&nbsp;Edward K.L. Chan","doi":"10.1016/j.jaut.2025.103503","DOIUrl":"10.1016/j.jaut.2025.103503","url":null,"abstract":"<div><div>Human autoantibodies have a long history of being valuable reagents to identify and characterize unique subcellular compartments, macromolecular complexes, and their individual components. One such discovery started as a unique cell-cycle related immunofluorescence pattern characterized as autoantibody targets localized in S and G2 phase nuclei of tissue culture cells, which became known as the “SG2NA” (SG2 nuclear antigen). These descriptions were followed by the identification of a calmodulin-binding protein family named ‘striatin’ that was later identified as three paralogs: Striatin/STRN1, Striatin-3/STRN3/SG2NA, and Striatin-4/STRN4/Zinedin. Many subsequent reports have used the designations SG2NA and striatin interchangeably. This report reviews the history of SG2NA and clarifies that striatin-3 is indeed a target autoantigen of some autoimmune sera, but commercially available striatin-3 antibodies or human sera that react with striatin-3 do not produce a SG2 phase nuclear staining pattern on HEp-2 cells. Hence, future reports should not use anti-SG2NA and anti-striatin interchangeably.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103503"},"PeriodicalIF":7.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584340","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":"Prior murine neurotropic coronavirus infection ameliorates experimental autoimmune encephalitis","authors":"Divyasha Saxena ,&nbsp;Kelly Walter ,&nbsp;Elizabeth Amona ,&nbsp;Maiying Kong ,&nbsp;Stanley Perlman ,&nbsp;Jian Zheng","doi":"10.1016/j.jaut.2025.103504","DOIUrl":"10.1016/j.jaut.2025.103504","url":null,"abstract":"<div><h3>Background</h3><div>Central nervous system (CNS) infections contribute to the development of neuroinflammation and neurodegenerative diseases. However, the mechanisms underlying the correlation between CNS infection and subsequent inflammatory course remain largely unknown.</div></div><div><h3>Methods</h3><div>Here, we addressed this question by infecting mice with a sublethal dose of a well-studied neurotropic coronavirus, mouse hepatitis virus (MHV), and investigated the effects of infection on the subsequent induction of a mouse multiple sclerosis (MS) model (myelin oligodendrocyte glycoprotein 35-55 (MOG_35-55) peptide-induced experimental autoimmune encephalitis (EAE)).</div></div><div><h3>Results</h3><div>Unexpectedly, C57BL/6J mice that recovered from MHV infection showed alleviated clinical signs of induced EAE. Mechanistically, this protection is mediated by a novel CNS-resident Foxp3⁺ CD8 T cell population induced by interleukin (IL)-10, which was secreted by myeloid cells that infiltrated the MHV-infected CNS as part of the MHV-specific immune response. These Foxp3⁺ CD8 T cells ameliorated EAE severity by decreasing the quantity and function of autoreactive CD4 and CD8 T cell infiltrating CNS independent of antigen specificity, as well as by inhibiting the activation of microglia accumulating in the affected spinal cords (SCs). The persistence of these Foxp3⁺ CD8 T cells in the CNS may contribute to the long-term post-acute sequelae of infection.</div></div><div><h3>Conclusion</h3><div>This study reveals a novel post-infectious anti-inflammatory milieu that develops in MHV-infected CNS of MHV and leads to the generation of Foxp3⁺ CD8 regulatory T cells, thereby diminishing the progression of subsequent autoimmune disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103504"},"PeriodicalIF":7.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584424","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":"The pivotal role of Interleukin-23 in the skin-gut-joint axis","authors":"Alen Zabotti ,&nbsp;Lucia Novelli ,&nbsp;Michele Maria Luchetti Gentiloni ,&nbsp;Giuliana Guggino ,&nbsp;Ana Biljan ,&nbsp;Ennio Lubrano ,&nbsp;Dennis McGonagle","doi":"10.1016/j.jaut.2025.103500","DOIUrl":"10.1016/j.jaut.2025.103500","url":null,"abstract":"<div><div>Interleukin-23 (IL-23) plays a pivotal role in the intricate interplay between the skin, gut, and joints, contributing significantly to the pathogenesis of various inflammatory diseases including psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD) and Behcet's disease. In recent years, several IL-23 inhibitors have been granted approval for the treatment of psoriasis, PsA and IBD. As up to one-third of patients diagnosed with psoriasis may go on to develop PsA and given the strong immunogenetic pathway incrimination of the IL-23 pathway in both psoriasis and PsA, dermatological lead therapy for psoriasis may therefore delay the development of PsA. Furthermore, patients with psoriasis or PsA are associated with increased risk of developing IBD. There is also evidence for psoriasis-directed therapy preventing IBD in keeping with the known pivotal role of IL-23 in both intestinal homeostasis and in the pathogenesis of IBD, including ulcerative colitis and Crohn's disease. This review discusses the multifaceted roles of IL-23 in regulating immune response and maintaining tissue homeostasis within the skin-gut-joint axis. In particular, the use of IL-23 inhibitors in trials in patients with psoriasis, IBD and PsA patients will also be discussed in relation to reverse translational immunology insights around inflammation in these domains.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103500"},"PeriodicalIF":7.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563125","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":"Temporal trajectories and DMARD therapy retention of rheumatoid arthritis patients with different autoimmune and inflammatory comorbidity profiles: a retrospective analysis","authors":"Signe Hässler ,&nbsp;Julie Aste ,&nbsp;Francis Berenbaum ,&nbsp;Michelle Rosenzwajg ,&nbsp;Jérémie Sellam ,&nbsp;David Klatzmann ,&nbsp;Milka Maravic","doi":"10.1016/j.jaut.2025.103502","DOIUrl":"10.1016/j.jaut.2025.103502","url":null,"abstract":"<div><h3>Background</h3><div>Patients with immunological diseases exhibit distinct comorbidity patterns, categorized into low comorbidity, polyautoimmunity, and polyinflammation profiles. This retrospective cohort study aimed to validate these profiles in rheumatoid arthritis (RA) patients, examine their longitudinal trajectories, and assess their impact on treatment persistence.</div></div><div><h3>Methods</h3><div>RA patients, and their associated treatments, were identified from the French pharmacy-dispensing database LRx through an algorithm based on targeted therapies. Algorithms to identify 17 comorbidities were designed based on drug indications. Comorbidity clusters were assigned yearly using a multinomial regression model, and state sequence analysis with hierarchical clustering was used to define their temporal trajectories. DMARD retention across comorbidity trajectories was evaluated through Cox regression models.</div></div><div><h3>Results</h3><div>Among 15,189 RA patients (maximum follow-up: 10 years), initial comorbidity profiles included low comorbidity (61.9 %), polyautoimmunity (24.7 %), and polyinflammation (13.4 %). Four trajectory patterns emerged among 5223 patients with at least 8 years of follow-up: stable low comorbidity (50 %), dominant polyautoimmune (31 %), stable polyinflammatory (9 %), and low comorbidity switching to polyinflammation (polyinflammation switchers, 10 %). The prevalence of polyautoimmunity and polyinflammation increased with age by 2.5 % [0.9 %–4.1 %] and 3.8 % [3.6 %–4.7 %] per decade, respectively.</div><div>Patients with stable polyinflammation had the lowest conventional synthetic DMARD 18-month persistence (stable polyinflammation: 15.68 % [10.26 %; 23.96 %]; polyinflammation switchers: 40.34 % [32.72 %; 49.75 %]; HR: 1.79 [1.33–2.42]). Stable low comorbidity patients had the highest biological and targeted synthetic DMARD persistence (polyinflammation switchers: 58.68 % [53.53 %; 64.32 %]; stable low comorbidity [65.66 % [63.20 %; 68.22 %]; aHR: 1.32 [1.09–1.60]).</div></div><div><h3>Conclusions</h3><div>Comorbidity trajectories in RA are associated with DMARD persistence, reflecting distinct subgroups with potential theranostic relevance. These results should be confirmed through a prospective study on DMARD-initiating patients.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103502"},"PeriodicalIF":7.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534342","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}