Journal of autoimmunity最新文献

{"title":"Stratifying patients by TNFSF13B genotype revealed increased flare and renal flare risk, but a greater benefit from belimumab: a potential biomarker for personalized treatment in systemic lupus erythematosus","authors":"Marta Paola Pireddu ,&nbsp;Giulia Rizzo ,&nbsp;Fabio Congiu ,&nbsp;Elisabetta Chessa ,&nbsp;Maristella Pitzalis ,&nbsp;Elena Ragusa ,&nbsp;Alberto Floris ,&nbsp;Francesca Deidda ,&nbsp;Mattia Congia ,&nbsp;Micaela Rita Naitza ,&nbsp;Maria Maddalena Angioni ,&nbsp;Francesco Cucca ,&nbsp;Alberto Cauli ,&nbsp;Matteo Piga","doi":"10.1016/j.jaut.2025.103455","DOIUrl":"10.1016/j.jaut.2025.103455","url":null,"abstract":"<div><h3>Objective</h3><div>To examine whether SLE patients carrying the TNFSF13B variant (BAFF-var) differ in the risk of overall and renal flares and the benefits from belimumab.</div></div><div><h3>Methods</h3><div>This retrospective study analyzed data from a monocentric cohort of Sardinian SLE patients between January 2006 and December 2022. We recorded demographic, clinical, serological, and treatment variables. A flare was defined as a new SLE manifestation or worsening of an existing one that required a change in therapy. Renal flares, categorized as nephritic or nephrotic, were recorded. Soluble B-cell activating factor (sBAFF) levels were evaluated in patients naïve to any treatment. We used Kaplan-Meier curves, Cox regression, and Poisson regression to investigate the association between BAFF-var and flares.</div></div><div><h3>Results</h3><div>Among 233 screened patients, 194 (89.2 % female, 61.3 % BAFF-var carriers) were included. The mean age was 41.1 (±14.8) years, and the mean number of follow-up visits was 17 (±8). sBAFF levels increased according to BAFF-var genotype (p &lt; 0.001). BAFF-var was significantly associated with an increased risk of flares (HR 1.5 per copy variant; 95 %CI 1.2–2.0; p = 0.002), and the frequency of flares (IRR 1.3 per copy variant; 95 %CI 1.1–1.6; p = 0.009). In 38 biopsy-confirmed lupus nephritis patients, the BAFF-var was associated with a higher risk of renal flare (HR 9.3; 95 %CI 1.7–49.5; p = 0.008). In 35 relapsing-remitting patients, belimumab reduced both the risk and frequency of flares, with higher effectiveness in patients carrying the BAFF-var (HR 0.12; 95 %CI 0.02–0.58; p = 0.009).</div></div><div><h3>Conclusions</h3><div>Pending further validation, BAFF-var may serve as a predictive and prognostic biomarker for personalized treatment in SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"155 ","pages":"Article 103455"},"PeriodicalIF":7.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517071","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":"STAT3 phosphorylation in the rheumatoid arthritis immunological synapse","authors":"Hila Novak-Kotzer ,&nbsp;Jesusa Capera ,&nbsp;Ashwin Jainarayanan ,&nbsp;Mirudula Elanchezhian ,&nbsp;Salvatore Valvo ,&nbsp;Viveka Mayya ,&nbsp;Alexandra Zanin-Zhorov ,&nbsp;Joanne Macdonald ,&nbsp;Peter C. Taylor ,&nbsp;Michael L. Dustin","doi":"10.1016/j.jaut.2025.103456","DOIUrl":"10.1016/j.jaut.2025.103456","url":null,"abstract":"<div><div>Targeting the JAK/STAT pathway has emerged as a key therapeutic strategy for managing Rheumatoid Arthritis (RA). JAK inhibitors suppress cytokine-mediated signaling, including the critical IL-6/STAT3 axis, thereby effectively targeting different aspects of the pathological process. However, despite their clinical efficacy, a subset of RA patients remains refractory to JAK inhibition, underscoring the need for alternative approaches. Here, we identify a novel JAK-independent mechanism of STAT3 activation, which is triggered by the formation of the immunological synapse (IS) in naive CD4⁺ T cells. Our data demonstrates that LCK mediates the TCR-dependent phosphorylation of STAT3 at the IS, highlighting this pathway as a previously unrecognized hallmark of early T cell activation. Furthermore, we show that the synaptic LCK/TCR-STAT3 pathway is compromised in RA. This discovery highlights a new therapeutic target for RA beyond JAK inhibitors, offering potential avenues for treating patients resistant to current therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"155 ","pages":"Article 103456"},"PeriodicalIF":7.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523846","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":"Association between occupational and environmental dust exposure and autoimmune diseases: A systematic review and meta-analysis","authors":"Seunghyun Lee ,&nbsp;Ah-Reum Jo ,&nbsp;Youjin Kim ,&nbsp;Wanhyung Lee ,&nbsp;Xiaoxue Ma","doi":"10.1016/j.jaut.2025.103440","DOIUrl":"10.1016/j.jaut.2025.103440","url":null,"abstract":"<div><h3>Background</h3><div>Occupational and environmental dust exposure is often overlooked, presenting significant public health concerns. Recent studies suggest it may increase the risk of autoimmune diseases. However, previous research has primarily focused on specific diseases or dust types, leaving the broader relationship unclear. A comprehensive meta-analysis are needed to clarify this connection.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed and Google Scholar up to October 2023, following PRISMA guidelines. Study quality was assessed using standard tools, and a random-effects model was used to estimate pooled odds ratio (OR) and 95 % confidence interval (CI), with subgroup analyses by dust type and disease category.</div></div><div><h3>Results</h3><div>From 90 initial records, 19 studies were included. Dust exposure was significantly associated with increased autoimmune disease risk (OR 1.36, 95 % CI 1.13–1.59). Both occupational (OR 1.18, 95 % CI 1.11–1.26) and environmental dust exposure (OR 1.12, 95 % CI 1.04–1.20) were linked to higher risk. Subgroup analysis showed a strong association between silica exposure and connective tissue diseases, particularly granulomatosis with polyangiitis (OR 5.75, 95 % CI 2.79–8.71). Sensitivity analysis confirmed the findings, though publication bias was noted.</div></div><div><h3>Conclusion</h3><div>Our findings highlight a significant association between dust exposure and autoimmune disease risk, underscoring the need for stricter occupational safety measures and environmental regulations. Targeted interventions, such as improved ventilation systems and personal protective equipment (PPE), should be prioritized. Future research should focus on elucidating underlying mechanisms to inform prevention and treatment strategies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103440"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131073","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 role of age-associated B cells in systemic lupus erythematosus","authors":"Qin-Yi Su ,&nbsp;Xin-Xin Zheng ,&nbsp;Xin-Ting Han ,&nbsp;Qian Li ,&nbsp;Ya-Ru Gao ,&nbsp;Sheng-Xiao Zhang ,&nbsp;Xiao-Feng Li","doi":"10.1016/j.jaut.2025.103433","DOIUrl":"10.1016/j.jaut.2025.103433","url":null,"abstract":"<div><div>Age-associated B cells (ABCs) are a distinct subset of B cells. This B-cell population expands in the elderly but is also abnormally expanded in patients with autoimmune diseases like systemic lupus erythematosus (SLE). ABC differentiation requires unique signaling stimuli, including BCR stimulation, TLR7 and TLR9 signaling, and the action of cytokines. The role of ABCs in the pathogenesis and treatment strategies of SLE has been a research hotspot in recent years. Possible pathogenic mechanisms include the production of autoantibodies and cytokines, as well as stimulation of spontaneous germinal center. Specifically targeting ABCs is a promising strategy for treating SLE. This article reviews the role of ABCs in SLE. Understanding the origin and differentiation of ABCs and their role in SLE will facilitate the discovery of novel drug targets for the treatment of SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103433"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912688","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":"PD1+ innate lymphoid cells 3 predict JAK-dependent inflammation in rheumatoid arthritis","authors":"Aditya Arra ,&nbsp;Katrin Vogel ,&nbsp;Irina Han ,&nbsp;Christine Behrendt ,&nbsp;Ildiko Rita Dunay ,&nbsp;Thomas Häupl ,&nbsp;Eugen Feist ,&nbsp;Monika C. Brunner-Weinzierl","doi":"10.1016/j.jaut.2025.103424","DOIUrl":"10.1016/j.jaut.2025.103424","url":null,"abstract":"<div><div>Innate lymphoid cells (ILCs) play a key role in maintaining immune homeostasis and are linked to inflammation and autoimmunity. This study investigates the role of ILCs in the pathogenesis of rheumatoid arthritis (RA) and their response to two targeted therapies - JAK inhibitors (JAKi), which block critical signaling pathways required for their activation, and TNF inhibitors (TNFi), which target a key inflammatory mediator - offering insights into how these interventions shape ILC-driven inflammation.</div><div>ILC distribution correlated with RA activity, as indicated by the DAS28 score, and this imbalance was improved significantly within four weeks of JAKi, underscoring its early therapeutic impact on ILC-mediated inflammation. While levels of ILC3-activating cytokines such as IL-1β and IL-23 declined under JAKi therapy, they remained unchanged with TNFi. Although JAKi and TNFi showed similar treatment efficacy, multivariate regression analysis showed that improvement in DAS28 score was strongly associated with increase in CTLA-4⁺ILC3 and reduction in both PD1⁺ILC3 frequency and systemic IL12p40/IL-23 levels only with JAKi. Notably, this two ILC3 subtypes determined the DAS28 score after 50 d of JAKi. In contrast, patients showing limited response to JAKi (ΔDAS28 &lt; 1.2) maintained high systemic IL-18 levels, a cytokine that induces signaling independent of the JAK pathway, suggesting a potential resistance mechanism. These findings highlight that monitoring PD1⁺ILC3s or IL-12p40/IL-23 may serve as an indicator of JAKi responsiveness, while elevated IL-18 may identify patients benefiting from alternative therapies. These results also emphasize the clinical relevance of targeting innate immunity for more personalized, pathway-focused RA therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103424"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882046","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":"Integrated analysis of polygenic and environmental risk scores for late-onset systemic lupus erythematosus","authors":"Mehmet Hocaoǧlu ,&nbsp;Amr H. Sawalha","doi":"10.1016/j.jaut.2025.103441","DOIUrl":"10.1016/j.jaut.2025.103441","url":null,"abstract":"<div><h3>Objective</h3><div>Polygenic risk scores (PRS) have been constructed to summarize genetic risk but there is limited research on environment-wide analysis of risk factors for systemic lupus erythematosus (SLE). In this study, we performed an environment-wide association study to construct an environmental risk score (ERS) for SLE and compare the risk conferred by ERS and PRS.</div></div><div><h3>Methods</h3><div>A total of 335 incident SLE cases were identified in the UK Biobank and matched 1:10 with age, sex, and ethnic background 3350 healthy controls. We examined the association between 37 environmental factors and SLE, using a univariate followed by a multivariate analysis. We summed the natural logarithm of the odds ratios (OR) of statistically significant environmental variables in the multivariable model to derive an ERS for SLE. Model discrimination was compared by De-Long′s test. PRS was calculated using the ORs of previously reported SLE genetic risk loci.</div></div><div><h3>Results</h3><div>The multivariate analysis revealed the association between daily sunlight exposure, depression, sleeplessness, sex hormone binding globulin levels, and air pollution with increased risk of SLE, while moderate physical activity was a protective factor. Increasing quartiles of the newly developed ERS were associated with similar degree of risk for SLE as the PRS. Integrating PRS with environmental factors significantly improved model performance.</div></div><div><h3>Conclusions</h3><div>We devised an ERS for SLE that summarizes the environmental component of the disease risk. We show that ERS confers a comparable degree of SLE risk as the PRS. Combining genetic and environmental factors could improve risk prediction models in SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103441"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147273","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":"VEXAS syndrome: A newly identified X-Linked hematoinflammatory disorder – A comprehensive overview of its genetic, molecular, inflammatory, and clinical landscape","authors":"Alpana Singh,&nbsp;Rishabh Chaudhary","doi":"10.1016/j.jaut.2025.103425","DOIUrl":"10.1016/j.jaut.2025.103425","url":null,"abstract":"<div><div>VEXAS (Vacuoles, E1 Enzyme, X-linked, Auto-inflammatory, Somatic) syndrome is a recently identified auto-inflammatory disorder predominantly affecting males over the age of 50. It arises due to somatic mutations in the <em>UBA1</em> gene, an X-linked gene essential for initiating the ubiquitin-proteasome system, leading to dysregulated protein degradation and immune dysfunction. Clinically, VEXAS presents with a diverse array of inflammatory manifestations, including persistent fever, neutrophilic dermatosis, auricular and nasal chondritis, pulmonary infiltrates, ocular inflammation, and venous thrombosis, along with significant haematological abnormalities such as macrocytic anemia, thrombocytopenia, myeloid and erythroid precursor vacuolization, and bone marrow dysplasia. These systemic complications contribute to high morbidity and mortality. Currently, therapeutic strategies remain largely undefined, with treatment focusing on two primary approaches, which are modulating inflammation through corticosteroids, JAK inhibitors, or IL-6 blockade and targeting the mutant hematopoietic clone or allogeneic hematopoietic stem cell transplantation (AHSCT) therapies. Supportive interventions, including red blood cell and platelet transfusions, erythropoiesis-stimulating agents, thromboprophylaxis, and antimicrobial prophylaxis, are crucial in managing disease-associated complications. This review aims to present a comprehensive analysis of VEXAS syndrome, focusing on its genetic underpinnings, pathophysiology, clinical manifestations, diagnostic criteria, and evolving therapeutic strategies. By integrating current findings from the literature and identifying gaps in ongoing research, this review seeks to equip clinicians and researchers with a comprehensive understanding of VEXAS syndrome. Additionally, it aims to guide future investigations toward refining diagnostic strategies, optimizing therapeutic approaches, and ultimately improving patient care and clinical outcomes.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103425"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886662","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":"HLA alleles predisposing to autoimmunity are linked to impaired immunoregulation in patients with juvenile autoimmune liver disease and in their first-degree relatives","authors":"Pengyun Wang ,&nbsp;Muhammed Yuksel ,&nbsp;Stella Gabeta ,&nbsp;Jonathon Graham ,&nbsp;Munther Hussain ,&nbsp;Laura Jayne Blackmore ,&nbsp;Xiaohong Huang ,&nbsp;Dino Hadzic ,&nbsp;Marianne Samyn ,&nbsp;Tassos Grammatikopoulos ,&nbsp;Michael Heneghan ,&nbsp;Rodrigo Liberal ,&nbsp;Maria Serena Longhi ,&nbsp;Giorgina Mieli-Vergani ,&nbsp;Diego Vergani ,&nbsp;Yun Ma","doi":"10.1016/j.jaut.2025.103436","DOIUrl":"10.1016/j.jaut.2025.103436","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Juvenile autoimmune liver disease (JAILD) comprises autoimmune hepatitis and autoimmune sclerosing cholangitis. JAILD-predisposing genes include HLA-DR3,DR7, DR13 and haplotype A1-B8-DR3. Mechanisms leading to liver autoimmunity remain elusive, though JAILD patients have aberrated immunoregulation. We investigated the influence of HLA genes on immune cells, focusing on T-cells and frequency and function of T regulatory cells (Tregs) in JAILD patients, their first-degree-relatives (FDRs) and healthy controls (HCs).</div></div><div><h3>Methods</h3><div>HLA class I and II genotypes were defined by PCR and peripheral blood mononuclear cells were immunophenotyped by FACS in 82 patients, 72 FDRs, 50 HCs. Treg function was tested by inhibition of CD4^posCD25^neg T-cell proliferation. Links between HLA genes, Treg frequency/function, pro-inflammatory/immunoregulatory cytokines, soluble and membrane-bound programmed cell death-1 (PD-1) were investigated.</div></div><div><h3>Results</h3><div>Proportion of subjects carrying HLA DR3/DR7/DR13 was 88 %, 92 %, 64 % in patients, FDRs and HCs. Circulating Treg frequency was lower in patients and FDRs than HCs. Inhibitory capacity of Tregs was lower in patients but similar in FDRs compared to HCs. FDRs possessing HLA DR3/DR7/DR13 genes had Treg frequencies lower than those without. PD-1 ^posCD4^pos T-cells were fewer in patients than HCs; PD-1^posCD8^pos T-cells were fewer in patients and FDRs than HCs. Patient plasma levels of IFN-γ were higher, and ratios of IFN-γ/IL-10 and IFN-γ/IL-2 lower than in HCs. All nine FDRs with autoimmune disorders had HLA DR3/DR7/DR13 genes and lower Treg frequency than those without autoimmune disorders and HCs.</div></div><div><h3>Conclusion</h3><div>We show a link between HLA disease-predisposing genes and defective immunoregulation not only in JAILD patients, but also in their FDRs, who are prone to autoimmune disorders.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103436"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912689","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":"Long-term outcomes of idiopathic inflammatory myopathies: a large-scale longitudinal cohort study","authors":"Yiran Chen ,&nbsp;Longyang Zhu ,&nbsp;Chen Zong ,&nbsp;Shiyu Wu ,&nbsp;Xinxin Zhang ,&nbsp;Lingling Huo ,&nbsp;Yongpeng Ge ,&nbsp;Xiaolan Tian ,&nbsp;Fang Chen ,&nbsp;Wei Jiang ,&nbsp;Sizhao Li ,&nbsp;Yu Zuo ,&nbsp;Shanshan Li ,&nbsp;Linrong He ,&nbsp;Chunjia Li ,&nbsp;Hanbo Yang ,&nbsp;Xinyue Xiao ,&nbsp;Lin Liang ,&nbsp;Xia Liu ,&nbsp;Lu Zhang ,&nbsp;Qinglin Peng","doi":"10.1016/j.jaut.2025.103435","DOIUrl":"10.1016/j.jaut.2025.103435","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate mortality, patient-reported outcomes (PROs), and drug-free remission (DFR) in a large well-characterised cohort of idiopathic inflammatory myopathies (IIMs).</div></div><div><h3>Methods</h3><div>This study retrospectively enrolled 1854 patients with IIMs. Follow-up lasted up to 20 years. Mortality was analysed using the standardised mortality ratio (SMR) and Kaplan-Meier survival analysis. PROs and DFR rates were examined in the survivors at the end of follow-up.</div></div><div><h3>Results</h3><div>Of 1854 patients, 348 (18.8 %) died during follow-up, with an overall SMR of 6.82 (95 % confidence interval [CI] 6.11–7.54). Subgroup analysis revealed the highest SMRs in dermatomyositis (DM), followed by antisynthetase syndrome (ASS), and immune-mediated necrotising myopathy, while SMRs in patients with polymyositis indicated no significant mortality difference from general population. Patients with anti-MDA5-positive DM exhibited higher SMRs than those with other IIM serotypes. Respiratory failure was the leading cause of death among patients with IIMs. Patients with DM had the lowest survival rates within the initial nine years of disease duration, whereas patients with ASS exhibited significantly reduced survival after nine years. At the end of follow-up, 17.1 % of patients achieved DFR (cumulative 3-, 5-, and 10-year DFR rates of 6.1 %, 14.9 %, and 29.3 %, respectively). Patients with DM presented with better PROs and higher DFR rates than those with other IIM subtypes.</div></div><div><h3>Conclusions</h3><div>Our data indicated increased mortality in patients with IIM compared with the general population and provided an important foundational understanding of IIMs. These findings emphasise the heterogeneity in the long-term outcomes across IIM subtypes, DM's acute nature, and ASS's progressive course.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103435"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906442","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 phenotypic and functional characteristics of intrahepatic CD69+CD103+ tissue-resident MAIT cells in primary biliary cholangitis","authors":"Qiyun Xia ,&nbsp;Zhuwan Lyu ,&nbsp;Yudong Zhao ,&nbsp;Xiting Pu ,&nbsp;Jian Wang ,&nbsp;Yuyang Liu ,&nbsp;Yujie Zhou ,&nbsp;Jun Qian ,&nbsp;M.E. Gershwin ,&nbsp;Min Lian ,&nbsp;Xiong Ma","doi":"10.1016/j.jaut.2025.103442","DOIUrl":"10.1016/j.jaut.2025.103442","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset that plays a significant role in the immunopathology of primary biliary cholangitis (PBC). However, our understanding of the subpopulations involved in hepatic residency have not been elucidated. Herein, our goal was to delineate the phenotypic and functional properties of intrahepatic tissue-resident MAIT cells in PBC.</div></div><div><h3>Methods</h3><div>Liver tissue and intrahepatic mononuclear cells were collected and analyzed by immunohistochemistry, immunofluorescence and flow cytometry. The transcriptome was determined using in vitro generated tissue-resident MAIT cells. FOXM1's immunoregulatory role was evaluated with inhibitor treatment and regulatory features of BHLHE40 were confirmed by CUT&amp;Tag-seq and luciferase assays.</div></div><div><h3>Results</h3><div>In PBC, the frequency of intrahepatic MAIT cell decreased, but tissue-resident (CD69⁺CD103⁺) MAIT cells significantly expanded and expressed a notably pro-inflammatory phenotype, with substantial elevated expression of CXCR3, CXCR6; IL-17A, IFN-γ and T-bet. FOXM1, a transcriptional factor governing cell proliferation cycle, exhibited notably higher expression in tissue-resident MAIT cells than in non-resident MAIT cells. Inhibition of FOXM1 compromised the in vitro expansion of MAIT cells, and impaired the expression of CXCR3, IL-17A, IFN-γ and GM-SCF by tissue-resident MAIT cells. CUT&amp;Tag-seq and luciferase assay revealed a direct regulation of FOXM1 of BHLHE40 expression.</div></div><div><h3>Conclusion</h3><div>Our data reveals a pro-inflammatory role of expanded tissue-resident MAIT cells in PBC mediated via higher expression of effector cytokines, chemokine receptors and a related transcriptional factor. FOXM1 critically regulates MAIT cell proliferation and tissue-resident pro-inflammatory function, via interaction with BHLHE40, and establishes a transcriptional axis linking proliferation to effector responses.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103442"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195607","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}