Journal of autoimmunity最新文献

{"title":"Interpretation of the association between thyroid peroxidase antibodies and thyroid function during pregnancy: An individual participant data meta-analysis","authors":"Yindi Liu , Joris A.J. Osinga , Ulla Feldt-Rasmussen , Tanja G.M. Vrijkotte , Peter N. Taylor , Ashraf Aminorroaya , Ghalia Ashoor , Sofie Bliddal , Liang-Miao Chen , Bijay Vaidya , Glenn E. Palomaki , Farkhanda Ghafoor , Abel López-Bermejo , Victor J.M. Pop , Sachiko Itoh , Fang-biao Tao , Lorena Mosso , Tuija Männistö , Kris G. Poppe , Elizabeth N. Pearce , Tim I.M. Korevaar","doi":"10.1016/j.jaut.2025.103491","DOIUrl":"10.1016/j.jaut.2025.103491","url":null,"abstract":"<div><h3>Background</h3><div>Thyroid peroxidase antibody (TPOAb) positivity is the most important risk factor for hypothyroidism and determines thyroid function follow-up during pregnancy. TPOAb positivity is usually defined by manufacturer cut-offs which typically derived from non-pregnant populations. However, as a state of immune tolerance, pregnancy can affect TPOAb concentrations. To improve the understanding of clinical relevance of TPOAb concentrations during pregnancy, we investigated the association of TPOAbs with maternal thyroid function.</div></div><div><h3>Methods</h3><div>We performed an individual participant data meta-analysis embedded in the Consortium on Thyroid and Pregnancy. Participants with multiple gestations, pre-existing thyroid disease, thyroid (interfering) medication usage, or conception by in vitro fertilization were excluded. We used mixed effects regression models to assess the association of TPOAb percentiles calculated in each cohort with maternal thyroid function.</div></div><div><h3>Results</h3><div>The study population comprised 62,634 pregnant women from 24 cohorts. As compared to TPOAb percentiles ≤80, there were progressively higher mean thyroid stimulating hormone (TSH) concentrations across TPOAb percentiles ≥89, with corresponding mean differences ranging from +0.11 SD (95 % confidence interval [CI] +0.04 SD, +0.19 SD) at the 89th percentile to +1.04 SD (95 % CI + 0.96 SD, 1.11 SD) at the 100th percentile. Higher TPOAb percentiles were associated with progressively lower mean free thyroxine (FT4) concentrations across TPOAb percentiles ≥91, with corresponding mean differences ranging from −0.08 SD (95 % CI -0.16 SD, −0.01 SD) at the 91st percentile to −0.48 SD (95 % CI -0.56 SD, −0.4 SD) at the 100th percentile. From the 89th TPOAb percentile upwards, there were progressively higher risks of TSH >4.0 mU/L, with absolute risks of 2.4 %, 4.0 %, and 28.1 % in cases of ≤80th, 89th, and 100th TPOAb percentiles, respectively. Higher TPOAb percentiles were also associated with lower thyroidal response to human chorionic gonadotropin stimulation and higher risks of overt and subclinical hypothyroidism. In 19 of the included cohorts, there were 0.4–6.3 % of pregnant women with TPOAb concentrations lower than the positivity cut-offs but larger than or equal to the 89th-percentile concentrations. The associations of TPOAbs with TSH and with FT4 were most apparent during early pregnancy (<em>P</em> for interaction <0.001 for both TSH and FT4).</div></div><div><h3>Conclusions</h3><div>During pregnancy, TPOAbs were dose-dependently associated with TSH, FT4, and the risk of abnormal thyroid function. With concentrations below currently used positivity cut-offs, TPOAbs could be associated with lower maternal thyroid function, which indicates clinically relevant thyroid autoimmunity. These findings implicates that high normal TPOAb concentrations upon first assessment in pregnancy may warrant active follow-up.</div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103491"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268017","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":"Comparative risk of rheumatoid arthritis between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in type 2 diabetes","authors":"Fu-Shun Yen ,&nbsp;Shiow-Ing Wang ,&nbsp;Chii-Min Hwu ,&nbsp;Chien-Wei Haung ,&nbsp;Renin Chang ,&nbsp;Chih-Cheng Hsu ,&nbsp;James Cheng-Chung Wei","doi":"10.1016/j.jaut.2025.103493","DOIUrl":"10.1016/j.jaut.2025.103493","url":null,"abstract":"<div><h3>Introduction</h3><div>Rheumatoid arthritis (RA) causes disability, chronic pain, and reduced quality of life. Preclinical studies suggest glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce inflammation and protect joint tissues. This study compared GLP-1 RAs with non-GLP-1 RAs on the risk of RA in patients with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>Using the TriNetX network (2016–2023), we identified 2,688,327 patients with T2DM. Propensity score matching yielded 89,938, 111,074, and 88,054 pairs of GLP-1 RA users versus dipeptidyl peptidase-4 inhibitors (DPP-4i), basal insulin, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), respectively. Analyses followed an as-treated approach. Relative hazards of RA were estimated with Kaplan–Meier methods. Subgroup analyses were performed, and a sensitivity analysis used the intention-to-treat approach.</div></div><div><h3>Results</h3><div>In matched cohorts, GLP-1 RAs showed no significant difference in 7-year RA risk versus DPP-4i (HR 1.06, 95 % CI 0.98–1.15) or basal insulin (HR 0.98, 95 % CI 0.89–1.08). By contrast, SGLT2i use was associated with lower RA risk compared with GLP-1 RAs (HR 0.88, 95 % CI 0.80–0.96). Kaplan–Meier curves confirmed a significantly lower cumulative incidence of RA in SGLT2i users (log-rank p = 0.007).</div></div><div><h3>Conclusions</h3><div>In this multicenter cohort study of patients with T2DM, GLP-1 RAs did not significantly alter RA risk compared with DPP-4i or basal insulin. In contrast, SGLT2i was associated with a significantly reduced risk of new-onset RA, suggesting potential anti-inflammatory benefits.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103493"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324703","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":"Mitochondrial dysfunction is a potential key mechanism for atherosclerosis predisposition in patients with systemic lupus erythematosus","authors":"Xinxin Liu,&nbsp;Chao Wang,&nbsp;Xiuru Guan","doi":"10.1016/j.jaut.2025.103488","DOIUrl":"10.1016/j.jaut.2025.103488","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and its course is often accompanied by multiple organ damage. The mortality rate of SLE exhibits a “bimodal pattern”, namely the early death peak is primarily attributed to infection and lupus activity, while the late death peak lists cardiovascular diseases (CVD) caused by atherosclerosis (AS) as the leading cause of death. Mitochondria, as the hub of energy metabolism and the multi-dimensional regulatory center of cellular functions, play a key role in the occurrence and development of AS plaques under the pathological background of SLE. This review systematically sorted out the mitochondrial dysfunction mechanisms of different immune cells and endothelial cells in SLE, and deeply expounded their influence pathways on the pathological process of AS. Furthermore, this article explores the current clinical treatment strategies for SLE and analyzes the therapeutic potential of mitochondrial-targeted intervention measures.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103488"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086318","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 concept of severity in psoriatic arthritis: a scoping review of the literature","authors":"Ennio Lubrano ,&nbsp;Mauro Fatica ,&nbsp;Rubén Queiro ,&nbsp;Fabio Massimo Perrotta","doi":"10.1016/j.jaut.2025.103494","DOIUrl":"10.1016/j.jaut.2025.103494","url":null,"abstract":"<div><h3>Objective</h3><div>The concept of severity in psoriatic arthritis (PsA) remains inconsistently defined, often conflated with disease activity. This scoping review aimed to explore how severity has been defined in the PsA literature and to identify criteria used to characterize severe disease.</div></div><div><h3>Methods</h3><div>A scoping review was conducted in April 2025 following PRISMA-ScR guidelines. PubMed was searched for English-language articles from the last 25 years, alongside abstracts from major rheumatology conferences. Eligible studies had to explicitly define or discuss PsA severity. Articles focusing solely on activity, isolated disease manifestations, or other conditions were excluded. Data were extracted on the type of article, definitions of severity, and criteria used.</div></div><div><h3>Results</h3><div>Of 4,014 records screened, 32 studies met inclusion criteria. Definitions of severity varied widely and were categorized into imaging (e.g., erosions), clinical (e.g., dactylitis, joint counts), and functional (e.g., HAQ-DI scores) criteria. The most commonly used indicators were structural damage, polyarticular involvement, dactylitis, arthritis mutilans, and validated composite indices such as CPDAI. Only a few studies incorporated functional impairment or patient-reported outcomes. While some guidelines, including GRAPPA and ACR/NPF, proposed multidomain frameworks, a standardized definition remains lacking.</div></div><div><h3>Conclusion</h3><div>The concept of PsA severity has evolved beyond mere disease activity to encompass long-term outcomes, radiographic damage and overall disease burden. However, considerable heterogeneity persists across studies, reflecting the complexity of PsA. A standardized, multidimensional definition of severity, distinct from disease activity, would enhance patient stratification, guide treatment decisions, and support clinical research.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103494"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358096","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":"Chimeric antigen receptor T cell therapy: a new frontier therapeutic landscape in autoimmune diseases","authors":"Xueting An ,&nbsp;Xiaoyu Huang","doi":"10.1016/j.jaut.2025.103495","DOIUrl":"10.1016/j.jaut.2025.103495","url":null,"abstract":"<div><div>Chimeric antigen receptor-T (CAR-T) cells are genetically engineered T cells that has demonstrated significant success in treating hematologic tumors. The therapeutic landscape of CAR-T cell therapy is undergoing paradigm-shifting expansion into autoimmune disease management. Emerging clinical evidence demonstrates that engineered CAR-T cells can achieve unprecedented disease remission in the treatment of autoimmune diseases by efficiently depleting autoreactive B cells, thereby resetting the immune system, while maintaining favorable safety profiles. These encouraging results have motivated in-depth exploration into expanding the application of CAR-T cells to a broader spectrum of autoimmune diseases, as well as the development of advanced cell products with better efficacy and safety. This review systematically explores fundamental research and clinical applications of CAR-T cell therapy in autoimmune diseases, critically examines existing limitations, and proposes potential future directions. Significantly, the study elucidates structural characteristics of disease-associated autoantigens in autoimmune diseases, offering novel perspectives and technical frameworks for developing next-generation chimeric autoantibody receptor-T (CAAR-T) therapeutics with enhanced precision.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103495"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358097","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":"Elderly-onset systemic sclerosis defines a distinct clinical subset: analysis from the SPRING registry of the Italian Society for Rheumatology","authors":"Antonio Tonutti ,&nbsp;Francesca Motta ,&nbsp;Gianluigi Bajocchi ,&nbsp;Silvia Bellando-Randone ,&nbsp;Cosimo Bruni ,&nbsp;Martina Orlandi ,&nbsp;Giovanni Zanframundo ,&nbsp;Roberta Foti ,&nbsp;Giovanna Cuomo ,&nbsp;Alarico Ariani ,&nbsp;Edoardo Rosato ,&nbsp;Gemma Lepri ,&nbsp;Francesco Girelli ,&nbsp;Elisabetta Zanatta ,&nbsp;Silvia Laura Bosello ,&nbsp;Ilaria Cavazzana ,&nbsp;Francesca Ingegnoli ,&nbsp;Fabio Cacciapaglia ,&nbsp;Giuseppe Murdaca ,&nbsp;Giuseppina Abignano ,&nbsp;Rossella De Angelis","doi":"10.1016/j.jaut.2025.103501","DOIUrl":"10.1016/j.jaut.2025.103501","url":null,"abstract":"<div><h3>Objective</h3><div>Elderly-onset systemic sclerosis (SSc) is relatively uncommon, and its clinical phenotype and prognostic implications remain poorly characterized, with conflicting evidence regarding disease course and outcomes.</div></div><div><h3>Methods</h3><div>Within the Italian SPRING (Systemic Sclerosis PRogression INvestiGation) registry, we compared demographic and clinical characteristics of patients with elderly-onset SSc (≥70 years at the time of the first non-Raynaud's manifestation) to those with younger onset. Cross-sectional analyses, multivariable logistic regression, and unsupervised cluster analysis were conducted to identify features associated with elderly-onset SSc. Longitudinal analysis was performed to assess mortality risk within SSc patients and compared to the general Italian population.</div></div><div><h3>Results</h3><div>Elderly-onset accounted for 8.5 % (160/1893) SSc cases in SPRING. These patients exhibited fewer peripheral vascular complications (digital ulcers: 13 % vs. 23 %; p = 0.016), higher prevalence of anticentromere antibodies (60 % vs. 39 %; p = 0.007), a lower prevalence and likelihood of diffuse skin subset (OR 0.40; 95 % CI 0.19–0.83) but an increased risk of pulmonary arterial hypertension confirmed on right-heart catheterization (OR 14.1; 95 % CI 3.68–54.5) at multivariate analysis. As expected, patients with elderly onset SSc had an increased risk of death compared to younger-onset individuals. Compared with the age-, sex-, and calendar year-matched general Italian population, patients with SSc showed a fivefold increased mortality, with a trend toward a higher risk in young-onset (SMR 6.3; 95 %CI 4.1–9.1) compared with elderly-onset (SMR 4.5; 95 %CI 2.4–7.7) cases.</div></div><div><h3>Conclusions</h3><div>Elderly-onset identifies a distinct clinical subset of SSc, mainly characterized by mild cutaneous and peripheral vascular involvement, but showing a greater burden of pulmonary vascular disease and increased mortality compared to the age-matched general population.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103501"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516875","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":"Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) in adults with moderately to severely active systemic lupus erythematosus: a phase I dose-escalation study","authors":"Yiyang Wang ,&nbsp;Shaoying Yang ,&nbsp;Ye Yu ,&nbsp;Peng Xia ,&nbsp;Cuiwei Xie ,&nbsp;Chunyan Zhang ,&nbsp;Liangjing Lu","doi":"10.1016/j.jaut.2025.103489","DOIUrl":"10.1016/j.jaut.2025.103489","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative treatment in autoimmune diseases. Relmacabtagene autoleucel (relma‐cel) is an autologous, CD19-directed CAR-T cell product developed with a commercial-ready process in China. This study evaluates the safety and efficacy of relma‐cel in patients with moderately to severely active systemic lupus erythematosus (SLE).</div></div><div><h3>Methods</h3><div>In this phase I, single-arm, dose escalation study, 8 female patients with moderately to severely active SLE were enrolled. All patients received a single infusion of relma‐cel at escalating doses (50 × 10⁶, 75 × 10⁶, or 100 × 10⁶ CAR-T cells) after preconditioning with fludarabine and cyclophosphamide. The primary endpoints included the incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs). Secondary endpoints comprised pharmacokinetics, pharmacodynamics, and efficacy, which was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), SLE Responder Index (SRI)-4, Lupus Low Disease Activity State (LLDAS), and Definition of Remission in SLE (DORIS) remission criteria.</div></div><div><h3>Results</h3><div>No dose-limiting toxicities were reported. Adverse events were manageable, with cytokine release syndrome (CRS) occurred in 7 patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 1 patient. The mean SLEDAI-2K score of patients decreased from 12.625 at baseline to 3.25 at follow-up. All patients achieved an SRI-4 response at 6 months, with 6 patients meeting LLDAS criteria and 5 achieving DORIS remission. Improvements in renal function and complement levels were also noted.</div></div><div><h3>Conclusions</h3><div>Relma-cel demonstrates a manageable safety profile and promising efficacy in patients with moderately to severely active SLE. A dose of 100 × 10⁶ CAR-T cells was identified as the recommended phase II dose based on clinical response and tolerability.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103489"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212819","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":"Lymphoma driver mutations at the root of somatic evolution of nerve-damaging autoantibodies in myelin associated glycoprotein neuropathy","authors":"Shane Kelly ,&nbsp;Mandeep Singh ,&nbsp;Amanda Russell ,&nbsp;Katherine J.L. Jackson ,&nbsp;Timothy J. Peters ,&nbsp;Andrew Carr ,&nbsp;Anthony D. Kelleher ,&nbsp;Matt Field ,&nbsp;Matthew Silsby ,&nbsp;Dan Suan ,&nbsp;Christopher C. Goodnow","doi":"10.1016/j.jaut.2025.103474","DOIUrl":"10.1016/j.jaut.2025.103474","url":null,"abstract":"<div><h3>Background</h3><div>In autoimmune disease it is not understood how self-reactive B cells escape immune tolerance checkpoints to produce pathogenic autoantibodies.</div></div><div><h3>Objective</h3><div>In patients with demyelinating polyneuropathy caused by IgM autoantibodies against myelin associated glycoprotein (MAG) and the sulphated trisaccharide CD57, we aimed to test the hypothesis that B cells making the autoantibody escaped tolerance by acquiring lymphoma driver somatic mutations.</div></div><div><h3>Methods</h3><div>Deep single-cell RNA, DNA, flow cytometric and antibody specificity analysis of blood from three patients with MAG neuropathy.</div></div><div><h3>Results</h3><div>MAG autoantibody-producing B cell clones exhibited extensive intraclonal immunoglobulin V(D)J hypermutation. In many of the sub-clonal branches, the replacement:silent ratio of V-region mutations was not different from that expected for unselected mutations, although in some branches the mutations either increased or eliminated binding to MAG and CD57 autoantigens. Prior to intraclonal V(D)J diversification, each clone had acquired a gain-of-function <em>MYD88</em>^{<em>p.L265P</em>} mutation, and some branches had acquired additional somatic mutations in <em>CXCR4, IGLL5</em> and <em>BTG2</em>. Whilst all MAG-binding clones harboured the <em>MYD88</em>^{<em>p.L265P</em>} mutation, the same mutation was also found in some control, polyclonal B cells. Deep sequencing of different blood cell subsets indicated <em>MYD88</em>^{<em>p.L265P</em>} was confined to B cells.</div></div><div><h3>Conclusion</h3><div>In three MAG neuropathy patients we find evidence that the self-reactive B cells responsible for their disease acquired a classical lymphoma driver somatic mutation early in their clonal expansion.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103474"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005150","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":"Methotrexate and low-dose prednisone in idiopathic retroperitoneal fibrosis: a randomised clinical trial","authors":"Francesco Peyronel ,&nbsp;Alessandra Palmisano ,&nbsp;Federica Maritati ,&nbsp;Federico Alberici ,&nbsp;Maria L. Urban ,&nbsp;Davide Gianfreda ,&nbsp;Giovanni M. Rossi ,&nbsp;Paride Fenaroli ,&nbsp;Alessandra Bettiol ,&nbsp;Gabriella Moroni ,&nbsp;Augusto Vaglio","doi":"10.1016/j.jaut.2025.103487","DOIUrl":"10.1016/j.jaut.2025.103487","url":null,"abstract":"<div><h3>Objectives</h3><div>To test the efficacy and safety of methotrexate plus low-dose prednisone in patients with idiopathic retroperitoneal fibrosis.</div></div><div><h3>Methods</h3><div>We conducted an open-label, randomised, active-controlled, non-inferiority phase III trial. Sixty (out of 78 screened) adults with newly diagnosed idiopathic retroperitoneal fibrosis and an estimated glomerular filtration rate &gt;30 mL/min/1.73 m² were enrolled at outpatient clinics of two Italian centres (Nephrology units of Parma University Hospital and Milano Policlinico Hospital). Patients were randomly assigned (1:1) to receive low-dose prednisone plus methotrexate (MTX + LowPred) or standard-dose prednisone alone (standPred) for nine months. The primary endpoint was remission at month 9. Remission was defined as absence of symptoms and ureteral obstruction (free of stents or nephrostomies), and normal acute-phase reactants; secondary endpoints included reduction in RPF thickness, relapses and treatment-related toxicity.</div></div><div><h3>Results</h3><div>29 patients received MTX + LowPred and 31 standPred. Twenty-six patients (89.7 %) receiving MTX + LowPred and 25 (80.6 %) receiving standPred achieved and maintained remission until month 9. The difference between remission rates was 9.1 % (95 %CI -9.9 %–27.3 %), meeting the criterion for non-inferiority. Time-to-remission was similar (log-rank test p = 0.549). The two groups showed comparable RPF thickness reduction and relapse rates. The median cumulative prednisone dose was significantly higher in the standPred group (p &lt; 0.001). No significant differences in adverse events were observed.</div></div><div><h3>Conclusions</h3><div>A low-dose prednisone plus methotrexate regimen is non-inferior to standard-dose prednisone in achieving remission in idiopathic retroperitoneal fibrosis, allowing significant reduction in glucocorticoid exposure.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov: NCT01240850.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103487"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099521","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":"Genetic susceptibility and validation of angiographic patterns in Takayasu arteritis","authors":"Desiré Casares-Marfil ,&nbsp;K. Bates Gribbons ,&nbsp;Guher Saruhan-Direskeneli ,&nbsp;Sema Kaymaz-Tahra ,&nbsp;Kaitlin A. Quinn ,&nbsp;Fatma Alibaz-Oner ,&nbsp;Peter C. Grayson ,&nbsp;Haner Direskeneli ,&nbsp;Amr H. Sawalha ,&nbsp;Peter A. Merkel","doi":"10.1016/j.jaut.2025.103496","DOIUrl":"10.1016/j.jaut.2025.103496","url":null,"abstract":"<div><h3>Background</h3><div>Prior studies identified subsets of patients with Takayasu arteritis (TAK) based on angiographic patterns of disease in cohorts from India and North America. This study aimed to validate these patterns in a TAK cohort from Turkey and determine the role of genetics in arterial patterns.</div></div><div><h3>Methods</h3><div>421 Turkish patients with TAK underwent angiography of the aorta and branch vessels, with disease involvement characterized in 13 arterial territories. K-means cluster analysis identified angiographically-based subgroups. 282 patients with TAK from Turkey and 115 European-American patients from North America were genotyped. Approximately 6.5 million SNPs were evaluated in a meta-analysis of both cohorts. Logistic regressions identified genetic associations with angiographic clusters (threshold for association: p-value&lt;1x10⁻⁵). Associated variants were functionally annotated.</div></div><div><h3>Results</h3><div>Three clusters were identified in Turkish patients, validating the previously-identified cluster pattern. Genome-wide meta-analyses revealed a locus in the solute carrier family gene <em>SLC24A2</em> in Cluster One as the most significant association (rs2891138, OR = 3.34, p-value = 2.32x10⁻⁷). Several genetic loci were associated with Cluster Two, including in <em>LGALSL</em> (rs883021, OR = 0.43, p-value = 1.00X10⁻⁵), <em>AK4P3</em> (rs1072778, OR = 0.39, p-value = 4.07X10⁻⁶), and <em>TMEM132B</em> (rs4765045, OR = 3.05, p-value = 6.18X10⁻⁶). The most significant locus associated with Cluster Three was in <em>FRMD6</em> (rs55692665, OR = 2.79, p-value = 1.11X10⁻⁷). Genetic effects were consistent between the cohorts. Several loci were associated with levels of mRNA expression in arterial tissues. A Cluster Two-associated variant in <em>APBB2</em> (rs2465578, OR = 0.35, p-value = 6.69x10⁻⁶) showed evidence for chromatin interaction with the <em>NSUN7</em> promoter and increased aortic <em>NSUN7</em> expression.</div></div><div><h3>Conclusions</h3><div>Genetic factors are associated with distinct subsets of TAK defined by angiographic pattern of disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"157 ","pages":"Article 103496"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145481841","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}