Arthritis & Rheumatology最新文献

{"title":"Comparative Safety of Common Immunosuppressant Therapies in Systemic Lupus Erythematosus: A Target Trial Emulation Study","authors":"Alí Duarte‐García, Marlon J. Sandino‐Bermúdez, Mariana González‐Treviño, Cynthia S. Crowson, Rozalina G. McCoy, Yihong Deng","doi":"10.1002/art.70343","DOIUrl":"https://doi.org/10.1002/art.70343","url":null,"abstract":"Objective Compare infection‐related hospitalization risk among patients with non‐renal SLE initiating commonly used immunosuppressants. Methods We emulated a target trial using Optum Labs Data Warehouse claims to compare the risk of infection‐related hospitalization among patients initiating azathioprine, belimumab, methotrexate, or mycophenolic acid analogues (MPAA) between March 2011 and September 2023. We excluded patients with prior lupus nephritis, solid‐organ or bone marrow transplantation, or rituximab/cyclophosphamide exposure. The primary outcome was time to first infection‐related hospitalization, using intention‐to‐treat (ITT) and per‐protocol (PP) analyses. We applied inverse probability of treatment weighting to account for baseline covariates and fitted marginal structural Cox models incorporating time‐varying monthly glucocorticoid dose during follow‐up. Results Among 6,168 patients, 24‐month cumulative incidence of infection‐related hospitalization was 10% (95%CI 8–12) for azathioprine, 8% (95%CI 5–10) for belimumab, 10% (95%CI 8–11) for methotrexate, and 13% (95%CI 10–15) for MPAA. In ITT analyses, MPAA had higher risk than belimumab (HR 1.55; 95%CI 1.07–2.25) and methotrexate (HR 1.32; 95%CI 1.04–1.68). In PP analyses, azathioprine (HR 2.04; 95%CI 1.01–4.16) and MPAA (HR 2.27; 95%CI 1.11–4.62) had higher risk compared with belimumab. After accounting for time‐varying monthly glucocorticoid dose, between‐treatment differences were no longer significant. Conclusions Initial differences in the infection‐related hospitalization risk were attenuated after accounting for time‐varying glucocorticoid exposure. These findings highlight glucocorticoid exposure as an important factor associated with serious infection risk, while recognizing that post‐baseline glucocorticoid use may reflect both evolving disease activity and a pathway through which therapies influence infection risk. <jats:boxed-text content-type=\"graphic\" position=\"anchor\"> <jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/art70343-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"15 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979468","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":"Incidence and Disease Course of Polymyalgia Rheumatica During Two Decades: A Nationwide Study Across Health Care Sectors in Denmark.","authors":"Agnete Overgaard Donskov, Ellen Margrethe Hauge, Annette De Thurah, Mette Nørgaard, Kresten Krarup Keller","doi":"10.1002/art.70337","DOIUrl":"10.1002/art.70337","url":null,"abstract":"<p><strong>Objective: </strong>A new algorithm enables the identification of patients with polymyalgia rheumatica (PMR) across health care sectors in Denmark. We estimated annual incidence rates from 2003 to 2024 and described the disease course, including the occurrence of late-onset giant cell arteritis (GCA) and prednisolone or prednisone (PDN) treatment.</p><p><strong>Methods: </strong>A Danish nationwide, population-based cohort study was conducted using data linked at the individual level. Cases were identified among people ages 50 years or older between January 1, 2003, and November 1, 2024.</p><p><strong>Results: </strong>A total of 51,401 patients were identified, including 24,456 from primary care and 26,945 from secondary care. The age-standardized incidence of PMR was 112 per 100,000 people (95% confidence interval [CI] 110.8-112.8). During the study period, the incidence declined by 53% in primary health care and increased by 30% in secondary health care, resulting in an overall decline of 12%. Among patients with PMR, GCA occurred at a rate of 5.4 (95% CI 5.1-5.7) per 1,000 patient-years, with a median of 68 days (interquartile range 10-602) from PMR diagnosis. Overall, 28% and 22% of patients were still treated with PDN after 5 and 10 years, with a median daily dose of 4.1 and 5.5 mg of PDN, respectively.</p><p><strong>Conclusion: </strong>The increasing incidence of PMR in secondary health care was exceeded by the declining incidence in primary health care. Most late-onset GCA developed within the first year after PMR diagnosis. Many patients continued treatment with PDN for 5 to 10 years, indicating a need for earlier use of concomitant therapies.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965742","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":"Longitudinal Changes in Cardiac Function Following Autologous Stem Cell Transplantation in Diffuse Systemic Sclerosis.","authors":"Jingjing He, Steele C Butcher, Xu Wang, Saad Ahmed, Jeroen J Bax, Jeska K de Vries-Bouwstra, Nina Ajmone Marsan","doi":"10.1002/art.70338","DOIUrl":"10.1002/art.70338","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular involvement is frequent in patients with systemic sclerosis (SSc). Autologous stem cell transplantation (ASCT) has emerged as a disease-modifying therapy for diffuse SSc, but its long-term impact on cardiac function remains unclear. We aim to examine the changes in left ventricular (LV) function after ASCT and their potential prognostic significance.</p><p><strong>Methods: </strong>From the Leiden Systemic Sclerosis cohort, 43 patients with diffuse SSc who underwent ASCT were matched 1:1 with controls with SSc based on sex, age, and disease duration. Patients with overt cardiac or pulmonary involvement were excluded. Serial echocardiography was performed annually, including LV ejection fraction (LVEF), global longitudinal strain (GLS), and diastolic parameters.</p><p><strong>Results: </strong>Among the included patients, mean age was 44.1 ± 10.5 years; 52.3% were female. At baseline, patients with ASCT showed mildly reduced LVEF (52.5% ± 9.1% vs 56.1% ± 6.3%, P = 0.044) and LV GLS (18.0% ± 2.6% vs 19.5% ± 2.5%, P = 0.014) compared to controls. During follow-up, ASCT was associated with significant improvement in LVEF (adjusted β = 1.59%/y, P < 0.001) and GLS (adjusted β = 0.71%/y, P < 0.001), whereas controls showed progressive decline. Diastolic parameters remained stable over time in both groups. Time-dependent changes in LV GLS, but not LVEF, were independently associated with all-cause mortality (adjusted hazard ratio 0.73 per %, 95% confidence interval 0.61-0.86, P = 0.0002).</p><p><strong>Conclusion: </strong>In patients with diffuse SSc, ASCT is associated with significant improvements in cardiac systolic function over time without adverse effects on diastolic function. These findings support the cardiac safety of ASCT, suggest potential cardiovascular benefit beyond systemic disease control, and highlight the importance of longitudinal monitoring with advanced echocardiography in SSc.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965793","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":"Clinical Images: Nasal-type extranodal natural killer/T cell lymphoma mimicking antineutrophil cytoplasmic antibody-associated vasculitis.","authors":"Hakeem Asad, Kenneth J Warrington","doi":"10.1002/art.70334","DOIUrl":"10.1002/art.70334","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962702","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":"Expert Perspectives: Toward Treat-to-Target Management in Adult Idiopathic Inflammatory Myopathies.","authors":"Shiri Keret, Nantakarn Pongtarakulpanit, Rohit Aggarwal","doi":"10.1002/art.70335","DOIUrl":"10.1002/art.70335","url":null,"abstract":"<p><p>Treat-to-target has transformed the management of several rheumatic diseases through predefined therapeutic goals, structured disease assessment, and timely treatment adjustment. Despite major advances in the understanding and treatment of idiopathic inflammatory myopathies (IIM), a formal treat-to-target framework for adult IIM has not yet been established. Given the substantial burden of persistent disease activity, treatment-related toxicity, and irreversible organ damage, together with recent advances in IIM therapeutics, there is increasing rationale for adopting a structured, target-oriented approach in these disorders. In this expert perspective, we discuss the principles of treat-to-target in adult IIM and review the evidence supporting its application. We examine key challenges that limit implementation, including the absence of validated definitions for remission and low disease activity, limitations of existing disease activity measures, the heterogeneity of clinical manifestations across organ systems, and the difficulty of distinguishing active inflammation from irreversible damage. We further discuss the role of skin, pulmonary, and patient-reported outcome assessments within a domain-based monitoring framework, together with practical considerations regarding biomarker interpretation and individualized treatment targets. Drawing on experience from other systemic autoimmune rheumatic diseases, we propose a pragmatic framework for treat-to-target implementation in adult IIM. This approach emphasizes measurable treatment goals, structured multidimensional assessment, shared decision-making, and adaptation of targets according to disease phenotype, organ involvement, and accumulated damage. Although important knowledge gaps remain, particularly regarding disease state definitions and outcome measure standardization, a treat-to-target strategy may improve disease control, reduce long-term morbidity, and provide a framework for clinical care and research in IIM.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962723","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":"Impact of Dual Interleukin-17A and Interleukin-17F Inhibition With Bimekizumab on Inflammatory and Structural Lesions in Axial Spondyloarthritis: Magnetic Resonance Imaging and Radiographic Outcomes From Two Phase 3 Studies and Their Open-Label Extension.","authors":"Walter P Maksymowych, Sofia Ramiro, Denis Poddubnyy, Xenofon Baraliakos, Robert G W Lambert, Ute Massow, Tom Vaux, Chetan Prajapati, Alexander Marten, Natasha de Peyrecave, Mikkel Østergaard","doi":"10.1002/art.70336","DOIUrl":"10.1002/art.70336","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of bimekizumab, a dual interleukin (IL)-17A and IL-17F inhibitor, on sacroiliac joints (SIJ) and spine inflammation/structural damage in axSpA using magnetic resonance imaging (MRI) scans/radiographs from the phase 3 studies BE MOBILE 1 (non-radiographic axSpA [nr-axSpA]) and 2 (radiographic axSpA [r-axSpA]) and their open-label extension (OLE).</p><p><strong>Methods: </strong>BE MOBILE 1 and 2 comprised 16-week double-blind placebo-controlled and 36-week maintenance periods. From week 16, all received subcutaneous bimekizumab 160 mg every 4 weeks. At week 52, patients could enter the OLE to continue bimekizumab. MRI scans were evaluated by treatment arm at baseline and weeks 16 and 52 in BE MOBILE 1 and 2 MRI substudies using Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ and Berlin spine inflammation scores, and SPARCC SIJ structural score (SSS; erosion, backfill, fat lesions, and ankylosis). In patients with baseline and week 104 radiographs, structural damage was assessed in the SIJ (modified New York [mNY] criteria; nr-axSpA) and spine (modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]; r-axSpA). Observed case data are reported.</p><p><strong>Results: </strong>At week 52, bimekizumab-randomized patients had substantially reduced inflammation (mean change from baseline [CfB]: SPARCC SIJ, nr-axSpA -7.6; r-axSpA -5.1; Berlin spine, nr-axSpA -0.5; r-axSpA -2.5), decreased erosion scores (nr-axSpA -1.8; r-axSpA -1.8), increased backfill (nr-axSpA 0.9; r-axSpA 0.6) and fat lesion scores (nr-axSpA 0.7; r-axSpA 0.5), and minimal changes in ankylosis (nr-axSpA 0.0; r-axSpA 0.2). With bimekizumab treatment to week 104, radiographs showed mean CfB of 0.03 in mNY (nr-axSpA) and mSASSS of 0.3 (r-axSpA).</p><p><strong>Conclusion: </strong>Dual inhibition of IL-17A and IL-17F with bimekizumab led to substantial reductions in MRI SIJ/spine inflammation, gradual decreases in SIJ erosion, and minimal radiographic progression in the SIJ/spine in patients with axSpA.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965767","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":"Local reasoning large language models for privacy‐preserving identification of systemic lupus erythematosus","authors":"Mehmet Hocaoǧlu, Amr H Sawalha","doi":"10.1002/art.70330","DOIUrl":"https://doi.org/10.1002/art.70330","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148915413","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":"Updated COVID-19 Vaccines and Health Outcomes in Patients With Autoimmune Rheumatic Conditions.","authors":"Lesley E Jackson, A Jerrod Anzalone, Kenneth G Saag, Rahima Begum, Akm F Rahman, Namrata Singh, Kaleb Michaud, Jasvinder A Singh, Rena C Patel, Maria I Danila","doi":"10.1002/art.70290","DOIUrl":"https://doi.org/10.1002/art.70290","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to assess the association between COVID-19 vaccination status and COVID-19-related hospital admissions, need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO), and death in people with autoimmune rheumatic conditions.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using National Clinical Cohort Collaborative (N3C) data on adults with autoimmune rheumatic conditions and incident COVID-19 occurring between December 2020 and August 2024. We assessed the association between COVID-19 vaccination status (unvaccinated, receipt of initial series, booster, or updated [2023-2024] vaccine) and COVID-19-related hospitalization (primary outcome), mechanical ventilation or ECMO, and death. Associations were estimated using mixed-effects logistic regression, adjusting for demographics, clinical risk, social vulnerability, and medications.</p><p><strong>Results: </strong>Our cohort included 60,980 patients with rheumatic conditions (median age 62 years), of whom 46,043 (76%) were female and 44,876 (74%) were non-Hispanic White. Overall, 6,336 (10%) had received an updated (2023-2024) COVID-19 vaccine. Adjusted odds of hospitalization decreased progressively with vaccination (initial series adjusted odds ratio [aOR] 0.59 [95% confidence interval (CI) 0.56-0.63]; boosted series aOR 0.29 [95% CI 0.27-0.31]; and updated series aOR 0.31 [95% CI 0.28-0.34]) compared with no vaccine doses. Among patients who had received only the initial vaccine series versus a booster/updated vaccine, the absolute risk reduction was 5.6%.</p><p><strong>Conclusion: </strong>We observed decreased odds of COVID-19-related hospitalizations among patients with autoimmune rheumatic conditions who received an updated COVID-19 or booster vaccine compared to those who received the initial series alone or were unvaccinated. Updated vaccinations provide significant protection for this medically vulnerable population and should be supported by clinicians, policymakers, and patient advocacy groups.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910274","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":"A Coding Single Nucleotide Polymorphism in β2‐Glycoprotein I (APOH) is Associated with Increased Autoantibody Levels but Reduced Venous Thromboembolism Risk","authors":"Christophe Lalaurie, Lili Liu, Atlas Khan, Chen Wang, Stephen S. Rich, R. Graham Barr, Elana J. Bernstein, Krzysztof Kiryluk, Thomas McDonnell, Yiming Luo","doi":"10.1002/art.70333","DOIUrl":"https://doi.org/10.1002/art.70333","url":null,"abstract":"Objective Anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies are central to antiphospholipid syndrome. The <jats:italic>APOH</jats:italic> locus has been associated with anti‐β2GPI, but the causal variant and thrombotic risk implications remain unclear. Methods We performed a multi‐ancestry genome‐wide association study (GWAS) of quantitative total anti‐β2GPI antibody levels in 5,969 participants from the Multi‐Ethnic Study of Atherosclerosis (MESA). The relationship between genetically determined anti‐β2GPI levels and venous thromboembolism (VTE) risk was evaluated using two‐sample Mendelian randomization (MR) and Bayesian colocalization. Candidate causal variants were prioritized by fine‐mapping and integrative functional genomic analyses. Molecular dynamics simulations were used to investigate the structural effects. Results We identified a genome‐wide significant association at the <jats:italic>APOH</jats:italic> locus (lead SNP rs1801690‐G, β = 0.21, p = 1.08 × 10 <jats:sup>‐10</jats:sup> ). Paradoxically, genetic variation at the <jats:italic>APOH</jats:italic> locus associated with higher anti‐β2GPI levels was associated with reduced VTE risk (β = −0.25, p = 3.95 × 10 <jats:sup>‐6</jats:sup> ; PP4 = 0.97), likely reflecting horizontal pleiotropy rather than a true protective antibody effect. Fine‐mapping and functional genomics prioritized the missense variant rs1801690 (W335S) as the most likely causal variant. Molecular dynamics simulations support a dual‐effect mechanism whereby W335S impairs phospholipid binding in Domain V while increasing epitope exposure in Domains I‐II. Conclusions The <jats:italic>APOH</jats:italic> genetic signal associated with higher anti‐β2GPI levels paradoxically reduced VTE risk, likely mediated by W335S via epitope accessibility and disrupted phospholipid binding. These findings provide human genetic evidence that phospholipid binding by DV is essential for anti‐β2GPI‐mediated thrombosis. The clinical utility of <jats:italic>APOH</jats:italic> genotype warrants further investigation.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"10 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148902289","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":"Inhibition of Endothelial BRD4 Alleviates Lupus Nephritis Partly Through Interacting With FLI-1.","authors":"Xuan Wang, Xian K Zhang, Caiyun Chen, Weiru Zhang, Xin Ni","doi":"10.1002/art.70324","DOIUrl":"10.1002/art.70324","url":null,"abstract":"<p><strong>Objective: </strong>Bromodomain 4 (BRD4) could be a therapeutic target in various diseases. We sought to investigate its role in lupus nephritis (LN) progression and explore whether targeting BRD4 could serve as a therapeutic approach for LN.</p><p><strong>Methods: </strong>BRD4 expression in renal cells was evaluated by immunofluorescence. Inhibition of endothelial BRD4 in mice was conducted by using BRD4 short hairpin RNA adeno-associated virus (shRNA-AAV) targeting endothelial cells (ECs). Mouse lupus models were MRL/Lpr mice. Human glomerular ECs (GECs) coupled with RNA sequencing, chromatin immunoprecipitation polymerase chain reaction, and protein-protein interaction assays were performed to define underlying mechanisms.</p><p><strong>Results: </strong>BRD4 expression was increased in renal ECs in patients with LN and in mouse lupus models. Bromodomain and extraterminal inhibitor NHWD870 treatment greatly improved the features of LN in MRL/Lpr mice as evidenced by reduced lesions, IgG and C3 deposition, immune infiltration, and improved ultrastructural morphology in renal tissues. BRD4 shRNA-AAV treatment robustly ameliorated the hallmark features of LN in MRL/Lpr mice including proteinuria, histologic and ultrastructural morphology of kidney, and IgG and C3 deposition and immune infiltration in kidney in MRL/Lpr mice. Elevated BRD4 led to changes in many pathways linked to LN and promoted permeability and immune responses in GECs, which were associated with their interaction with FLI-1. BRD4 shRNA-AAV treatment attenuated FLI-1 expression in MRL/Lpr mice. BRD4 and FLI-1 were colocalized in renal ECs, and FLI-1 expression was elevated in patients with LN.</p><p><strong>Conclusion: </strong>Elevated BRD4 in ECs is involved in LN pathogenesis, which is partly associated with its interaction with FLI-1. Targeting endothelial BRD4 could be a therapeutic strategy for LN.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899835","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}