Annals of the Rheumatic Diseases最新文献

{"title":"BCMA-targeted CAR T cell therapy can effectively induce disease remission in refractory lupus nephritis.","authors":"Ziwei Hu, Shaozhe Cai, Yikai Yu, Yu Chen, Bei Wang, Di Wang, Rui Zeng, Xiaofeng He, Guifen Shen, Fei Yu, Zhipeng Zeng, Yuxue Chen, Xiaofang Luo, Ziyun Zhang, Peiling Zhang, Hui Xiong, Lin Bai, Ping Ye, Shengyan Lin, Jishuai Zhang, Cong Ye, Chunrui Li, Lingli Dong","doi":"10.1016/j.ard.2025.06.2128","DOIUrl":"10.1016/j.ard.2025.06.2128","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to evaluate the safety and efficacy of anti-B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells in treating refractory lupus nephritis (LN).</p><p><strong>Methods: </strong>This is an open-label, single-arm clinical trial assessing anti-BCMA CAR T cells in treating refractory LN patients. CAR T cells were infused following lymphodepletion therapy with cyclophosphamide and fludarabine. Patients were regularly followed up, in which clinical assessments were performed and laboratory indices were collected. Repeated renal biopsies and single cell RNA sequencing in certain patients were performed to help evaluate the therapeutic efficacy. The primary endpoints were the safe dosage of single infusion and the occurrence of adverse events, while the secondary endpoints focused on the therapeutic efficacy (eg, changes of Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2000]).</p><p><strong>Results: </strong>Seven biopsy-confirmed LN patients were enrolled in this study with a median follow-up of 9 months, whose peripheral B cells were effectively eliminated within the first month postinfusions and restored within 3 months except one patient. Hypogammaglobulinemia was frequently observed in this study. Only one case of grade 1 cytokine release syndrome was noted, and no immune effector cell-associated neurotoxicity syndrome or severe infection was reported. SLEDAI-2K scores decreased from a median of 18 (range 10-22) at baseline to 0 (range 0-4) at the last follow-up, and 5 out of 7 patients achieved definition of remission in systemic lupus erythematosus (DORIS) complete remission. Decreased deposition of immune complex, reduced clonal abundance, and alleviated proinflammatory status of peripheral lymphocytes were also observed in repeated renal biopsy and transcriptomic analyses,.</p><p><strong>Conclusions: </strong>Anti-BCMA CAR T therapy can help LN patients inducing and maintaining disease remission status safely and effectively, which indicated the potential feasibility of the BCMA-only-targeting strategy in treating autoimmune diseases with abnormal humoral immune responses through CAR products.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1675-1683"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666885","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":"Response to correspondence on: Pulmonary arterial hypertension in adults with Still's disease: another pulmonary manifestation associated with HLA-DRB1*15.","authors":"Stéphane Mitrovic, Athénaïs Boucly, Olivier Sitbon, Bruno Fautrel, David Montani","doi":"10.1016/j.ard.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.ard.2025.07.003","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 10","pages":"e53-e55"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224788","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":"Correspondence on 'Pulmonary arterial hypertension in adults with Still's disease: another pulmonary manifestation associated with HLA-DRB1*15'.","authors":"Vivian E Saper, Ruud H J Verstegen, Gail H Deutsch","doi":"10.1016/j.ard.2025.06.2127","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2127","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 10","pages":"e50-e52"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224850","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":"Global recruitment patterns and placebo responses in clinical trials of rheumatoid arthritis.","authors":"Andreas Kerschbaumer, Marlene Steiner, Pascale Pruckner, Brigitte Wildner, Magdalena Maad, Josef S Smolen, Daniel Aletaha","doi":"10.1016/j.ard.2025.07.010","DOIUrl":"10.1016/j.ard.2025.07.010","url":null,"abstract":"<p><strong>Objectives: </strong>Placebo effects pose significant challenges in clinical trials for rheumatoid arthritis (RA). Understanding how socioeconomic factors of recruiting countries influence placebo responses is crucial for improving clinical trial design and outcomes. Here, we investigated the impact of global recruitment patterns on placebo responses in randomised controlled trials of RA.</p><p><strong>Methods: </strong>We analysed 124 trials (14 272 patients) investigating targeted therapeutics in RA and assessed how global recruitment patterns are related to placebo response rates using the per-capita gross national income (GNI; weighted by recruiting centres/country) as proxy for socioeconomic status in linear mixed models. Primary outcome was the American College of Rheumatology 20% response placebo response rate. Other socioeconomic metrics utilised were the Human Development Index and out-of-pocket health expenditures. Findings were validated using patient-level data from one global in randomised controlled trial.</p><p><strong>Results: </strong>We identified a negative association of GNI and placebo response rates across all trials (β = -3.7% placebo response per 10 000 international dollars; 95% CI: -5.61 to -1.80; P < .001). Results were confirmed using alternative metrics as well as using geographic data on individual patient level. Importantly, we could demonstrate a meaningful difference of this association when compared to active treatment responses.</p><p><strong>Conclusions: </strong>Our findings indicate that recruiting patients from lower-income countries is associated with higher placebo response rates, whereas active treatment responses remain stable. This may be driven by incentives to recruit patients into trials, such as limited access to therapies in less affluent countries. Addressing these factors is critical for improving trial design and ensuring accurate efficacy assessments.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1632-1640"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768317","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":"Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature.","authors":"Aris E Syntakas, Melissa Kartawinata, Nia M L Evans, Huong D Nguyen, Charalampia Papadopoulou, Muthana Al Obaidi, Clarissa Pilkington, Yvonne Glackin, Christopher B Mahony, Adam P Croft, Simon Eaton, Mario Cortina-Borja, Olumide Ogunbiyi, Ashirwad Merve, Lucy R Wedderburn, Meredyth G Ll Wilkinson","doi":"10.1016/j.ard.2025.07.015","DOIUrl":"10.1016/j.ard.2025.07.015","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the spatial transcriptomic landscape of muscle tissue from patients with treatment-naive juvenile dermatomyositis (JDM) in comparison to healthy paediatric muscle tissue.</p><p><strong>Methods: </strong>Muscle biopsies from 3 patients with JDM and 3 age-matched controls were analysed using the Nanostring GeoMx Digital Spatial Profiler. Regions of interest were selected based on muscle fibres without immune cells, immune cell infiltration and CD68+ macrophage enrichment. Differential gene expression, pathway analysis and pathways clustering analysis were conducted. Key findings were validated in 19 cases of JDM using immunohistochemistry and chemical stains, and a bulk RNAseq dataset of 4 cases of JDM.</p><p><strong>Results: </strong>JDM muscle tissues exhibited significant interferon pathway activation and mitochondrial dysfunction compared to controls. A 15-gene interferon signature was significantly elevated in JDM muscle and macrophage-enriched regions, correlating with clinical weakness. In contrast, mitochondrial dysregulation, characterised by downregulated respiratory chain pathways, was present regardless of interferon activity or muscle strength. The interferon-driven and mitochondrial signatures were replicated in an independent RNAseq dataset from JDM muscle; the lack of association between interferon signature and mitochondrial dysregulation was validated in 19 cases by conventional staining methods. Clustering analysis revealed distinct transcriptomic profiles between JDM and control tissues, as well as between patients with JDM with varying clinical phenotypes.</p><p><strong>Conclusions: </strong>This study highlights mitochondrial dysfunction as a consistent pathological feature in JDM muscle, which may be independent of interferon-driven inflammation. These findings highlight the potential for mitochondrial-targeted therapies in JDM management and emphasise the need for further studies to explore their therapeutic value.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1706-1720"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815730","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":"Mycophenolate mofetil plus methotrexate versus cyclophosphamide with sequential azathioprine for treatment of Takayasu arteritis.","authors":"Xiaochuan Sun, Jing Li, Xinwang Duan, Yahong Wang, Yu Chen, Ying Wang, Liyun Zhang, Dongyun Yao, Jing Xue, Zhenbiao Wu, Yi Zhao, Li Luo, Hongfeng Zhang, Xiuling Zhang, Lili Pan, Xiaofeng Zeng, Mengtao Li, Peter A Merkel, Xinping Tian","doi":"10.1016/j.ard.2025.07.018","DOIUrl":"10.1016/j.ard.2025.07.018","url":null,"abstract":"<p><strong>Objectives: </strong>Study the efficacy and safety of mycophenolate mofetil (MMF) combined with methotrexate (MTX) compared to cyclophosphamide (CYC) followed by azathioprine (AZA) to treat active Takayasu arteritis (TAK).</p><p><strong>Methods: </strong>Adults with active TAK were randomised in a 2:1 ratio to receive oral MMF plus MTX or intravenous CYC followed by oral AZA. All subjects also received high-dose oral glucocorticoids with a predefined taper. The primary endpoint was overall response rate at week 52, defined as achieving a complete response (CR) or partial response (PR). Secondary endpoints included rates of CR and PR at weeks 28 and 52.</p><p><strong>Results: </strong>A total of 111 patients with TAK were enrolled: 74 in the MMF+MTX group and 37 in the CYC/AZA group, with comparable baseline demographic and clinical features. The overall response rates at 28 and 52 weeks were 58.1% and 55.4% in the MMF+MTX group, respectively, higher than 32.4% at both time points in the CYC/AZA group (P = .011 and .022). CR and PR rates at 28 and 52 weeks were also higher in the MMF+MTX group. Relapse occurred in 4 patients in the MMF+MTX group and 2 in the CYC/AZA group. One serious adverse event, neutropenia with fever, occurred in 1 patient in the CYC/AZA group.</p><p><strong>Conclusions: </strong>Treatment of active TAK with MMF+MTX has more favourable efficacy compared to CYC/AZA. These findings provide evidence to use the combination of MTX and MMF, 2 generally well-tolerated and inexpensive therapies, to treat TAK.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1733-1742"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940130","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":"Response to correspondence about our article Hernández-Cruz B, Otero-Varela L, Freire-González M, Busquets-Pérez N, García González AJ, Moreno-Ramos M, et al. Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry. Ann Rheum Dis. 2024 Aug 27;83(9):1189-99. doi:10.1136/ard-2023-225271.","authors":"Blanca Hernández-Cruz","doi":"10.1016/j.ard.2025.08.022","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.022","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205479","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":"Short-chain fatty acids and their gut microbial pathways distinguish rheumatoid arthritis in discordant monozygotic twins.","authors":"Rebecca B Blank, Kevin Bu, Xinyuan Zhang, Weixi Chen, Ian Cunningham, Jeremy Sokolove, Lauren Lahey, Adriana Heguy, Rhina Medina, Carles Ubeda, Renuka R Nayak, Jiyuan Hu, Adam Cantor, Jakleen Lee, Frances M K Williams, Jose C Clemente, Jose U Scher","doi":"10.1016/j.ard.2025.08.029","DOIUrl":"10.1016/j.ard.2025.08.029","url":null,"abstract":"<p><strong>Objectives: </strong>Although genetic risk factors, such as HLA-DRB1 alleles, contribute to the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other factors are involved in disease development. Further, the relative contribution of nongenetic elements in identical twins has not been characterised. Here, we aimed to characterise host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multiomics approach.</p><p><strong>Methods: </strong>Eight pairs of MZ twins discordant for RA (N = 16) were enrolled in the United States (US). The gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and plasma proteins were measured in both plasma and faeces. Levels of short-chain fatty acids (SCFAs) from serum and faeces were quantified using gas chromatography mass spectrometry (GC-MS). Metagenomic data from a UK twin registry (TwinsUK) (N = 14) were used to validate findings in the US population.</p><p><strong>Results: </strong>Although microbiome diversity and composition did not differ between twins, we observed a significant decrease in the SCFA-producing bacteria Blautia faecis and significantly lower concentrations of faecal butyrate and propionate in affected RA twins in the US. TwinsUK showed a similar reduction in the SCFA-producers Gemmiger formicilis and Faecalicatena fissicatena, as well as bacterial SCFA metabolism pathways.</p><p><strong>Conclusions: </strong>Multiomics biomarkers differentiate MZ twins discordant for RA. Faecal butyrate and propionate, as well as SCFA-producing bacteria, were decreased in affected twins. We found a similar decrease in SCFA-producing taxa in affected twins in a geographically distinct cohort in the UK. Our results suggest that, if further validated in larger cohorts, multiomics approaches may improve our understanding of RA pathogenesis and, potentially, contribute to more accurate diagnostics and coadjuvant therapies.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197937","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":"Development and validation of a Disease Activity index for PSoriatic Arthritis based on 44 joints (DAPSA44).","authors":"Dafne Capelusnik, Clementina Lopez-Medina, Désirée van der Heijde, Daniel Aletaha, Josef Smolen, Anna Molto, Sofia Ramiro","doi":"10.1016/j.ard.2025.08.027","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.027","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to develop a modified Disease Activity index for PSoriatic Arthritis (DAPSA) score using the 44-joint count instead of the 66 swollen/68 tender joint counts (SJC/TJC) in patients with spondyloarthritis (SpA) (axial SpA [axSpA], peripheral SpA [pSpA], and psoriatic arthritis [PsA]) and evaluate its construct validity.</p><p><strong>Methods: </strong>Patients with axSpA, pSpA, and PsA included in the Assessment of SpondyloArthritis international Society-PerSpA (PERipheral involvement in SpondyloArthritis) study were randomly allocated 1:2 stratified for diagnosis and country into a derivation and validation cohort. For all patients, the 66SJC/68TJC were available, from which the SJC44/TJC44 were extracted. The derivation cohort was used to calculate the conversion factors for SJC66/TJC68 into SJC44/TJC44 to obtain the DAPSA44 using mixed-effects linear regression models. The validation cohort assessed the DAPSA44 construct validity through the agreement between continuous original-DAPSA/DAPSA44 (intraclass correlation coefficient [ICC]) and DAPSA disease activity states (weighted-kappa), Bland-Altman plot, Spearman correlations between original-DAPSA/DAPSA44 and external constructs, and discrimination between known groups (standardised mean differences [SMDs]) after stratifying patients into active/inactive based on a combination of patient global assessment (≥5/<5) and SJC (≥1/0 or ≥2/<2).</p><p><strong>Results: </strong>A total of 4121 patients (65% axSpA, 10% pSpA, and 25% PsA) were included. Conversion factors from the derivation cohort (n = 1364) for TJC and SJC were 1.30 and 1.34, respectively. The validation cohort (n = 2757) analyses showed almost-perfect agreement between original-DAPSA and DAPSA44 (ICC 0.98, kappa 0.95). Spearman correlation coefficients between DAPSA44 and external constructs fell within the predefined 0.3-wide range of corresponding original-DAPSA coefficients. DAPSA44 demonstrated excellent discriminatory ability (SMD > 0.8) across all scenarios of active/inactive disease.</p><p><strong>Conclusions: </strong>These findings support the use of DAPSA44 as a comparable tool to the original DAPSA for assessing disease activity due to peripheral arthritis in SpA, especially in situations where only a reduced joint count is available.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172627","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":"Augmentation of immunothrombosis as a key mechanism underlying JAK inhibition associated hypercoagulability in rheumatoid arthritis.","authors":"Paula David, Tom Macleod, Ala Altaie, Yu Shi, Kerem Abacar, Sami Giryes, Gabrielle de Mello Santos, Payal Ganguly, Mark Harland, Chi Wong, Andrew Scarsbrook, Paul Emery, Kulveer Mankia, Shouvik Dass, Andrea Di Matteo, Benazir Saleem, Cédric Duval, Robert Ariëns, Dennis McGonagle","doi":"10.1016/j.ard.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.ard.2025.09.002","url":null,"abstract":"<p><strong>Objectives: </strong>Venous thromboembolism (VTE), following Janus kinase inhibitors treatment (JAKi), is poorly understood in rheumatoid arthritis (RA). We investigated whether JAKi augmented immune cell-driven clotting or immunothrombosis in RA.</p><p><strong>Methods: </strong>Peripheral blood leukocytes (PBLs) isolated from patients with RA and healthy controls were treated with various JAKi classes, before stimulation with Toll-like receptor (TLR)-4 (lipopolysaccharide [LPS]) or TLR3 (polyinosinic-polycytidylic acid-poly (I:C)) agonists. Conditioned supernatants were used in plasma turbidity assays to evaluate clot formation and lysis dynamics, while bulk RNA sequencing, enzyme-linked immunosorbent assay, and bead-based immunoassays were used to explore immunothrombosis mechanisms.</p><p><strong>Results: </strong>Turbidity analyses showed that conditioned media from PBLs treated with LPS and tofacitinib significantly accelerated clot formation when compared to LPS alone, and this effect was tissue factor pathway dependent and accompanied by elevations in immunothrombotic cytokines, including tumour necrosis factor α, interleukin (IL)-1β, and IL-6. PBLs from patients with active RA exhibited significantly greater immunothrombotic potential compared to those with low disease activity, despite comparable baseline cytokine levels. RNA sequencing analysis revealed significant pathway enrichment in tofacitinib/LPS-treated PBLs, including activation of Nuclear Factor (NF)-κB pathways, increased tissue factor expression, and reduced levels of anticoagulant factors such as protein S. Pharmacological inhibition assays with 5 JAK therapies suggested that JAK1/tyrosine kinase 2-dependent effect underscored increased thrombosis but selective JAK3 inhibition did not reproduce the prothrombotic effects. Finally, patients with RA with JAK-associated pulmonary embolism showed interstitial changes compatible with immunothrombosis in 4/6 (67%).</p><p><strong>Conclusions: </strong>Immunothrombosis offers a novel explanation for JAKi-associated VTE in RA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172655","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}