Arthritis & Rheumatology最新文献

{"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}

{"title":"AMETHYST: A Retrospective Cohort Study of Treatment Patterns and Outcomes in Patients With Glucocorticoid-Refractory Macrophage Activation Syndrome Complicating Still's Disease.","authors":"Alexei Grom, Jordi Antón, Edward M Behrens, Corey Best, Norbert Blank, Josefin Blomkvist, Scott W Canna, Sonia Carriquí, Shanmuganathan Chandrakasan, Andrew Danquah, Ngoc-Bao Duong, Brian D Jamieson, Paivi Miettunen, Abiola Oladapo, Sampath Prahalad, Pierre Quartier, Grant Schulert, Anna Stoltenberg, Uwe Ullmann, Erika Van Nieuwenhove, Sebastiaan J Vastert, Fabrizio De Benedetti","doi":"10.1002/art.70326","DOIUrl":"10.1002/art.70326","url":null,"abstract":"<p><strong>Objective: </strong>Information is limited on the natural history and current treatment patterns in macrophage activation syndrome (MAS), a life-threatening hyperinflammatory syndrome complicating Still's disease (systemic juvenile idiopathic arthritis [sJIA] and adult-onset Still's disease [AOSD]). AMETHYST aimed to describe real-world treatment patterns and outcomes in glucocorticoid (GC)-refractory MAS complicating Still's disease.</p><p><strong>Methods: </strong>In this retrospective cohort study, medical data from January 1, 2012, to March 31, 2023, were abstracted from charts of all eligible patients across eight sites in Europe, Canada, and the United States for index MAS episodes (occurring between January 1, 2012, and September 30, 2022, and meeting eligibility criteria).</p><p><strong>Results: </strong>Overall, 55 of 64 included patients (86%) had sJIA and 9 of 64 (14%) had AOSD. Most patients (53/64 [82.8%]) were children at index (median age: 7.0 years). MAS was characterized by rash (60.4%), fever (52.8%), and hepatic involvement (49.1%). All patients received GCs; most were also treated with anakinra (48/64 [75%]) and/or ciclosporin (33/64 [51.6%]). Normalization of seven (complete MAS laboratory remission) or at least three (partial remission) prespecified laboratory parameters occurred in 7 of 64 (10.9%) and 41 of 64 patients (64.1%), respectively. GCs were tapered in 50 of 64 patients (78.1%) (median: 39.9 days). Per investigator assessment of clinical signs/symptoms for the index MAS episode, 24 of 64 (37.5%) and 26 of 64 patients (40.6%) had a complete and partial response, respectively. MAS recurred in 20 of 64 patients (31.3%). Seven of 64 patients (10.9%) died, and the estimated one-year survival probability was 93.75%.</p><p><strong>Conclusions: </strong>Low MAS laboratory remission rates and toxicities of high-dose GCs combined with other treatments highlight the need for safer, more effective therapies.</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":"148899840","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 synergistic impact of granulocytic myeloid-derived suppressor cells and innate lymphoid cells in systemic sclerosis.","authors":"Stefanie Weber, Mario R Angeli, Hashem Mohammadian, Hannah Labinsky, Maria Gabriella Raimondo, Richard Demmler, Yuko Ariza, Thomas Wohlfahrt, Markus Luber, Yi-Nan Li, Jörg H W Distler, Tobias Bäuerle, Georg Schett, Simon Rauber, Andreas Ramming, Alina M Ramming","doi":"10.1002/art.70325","DOIUrl":"10.1002/art.70325","url":null,"abstract":"<p><strong>Objective: </strong>Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by immune dysregulation and fibrosis, with myeloid-derived suppressor cells (MDSCs) emerging as important regulators of immune responses. However, the role of MDSCs in SSc-associated fibrosis and their interactions with other immune cell populations remain poorly understood.</p><p><strong>Methods: </strong>Peripheral blood (SSc: N=37, healthy: N=27) and skin biopsies (SSc: N=9, healthy: N=5) were analyzed using flow cytometry and fluorescence microscopy, respectively. Bleomycin-induced mouse models of fibrosis were used to validate findings, including pharmacological disruption of granulocytic MDSC (G-MDSC) activity via Bruton's tyrosine kinase inhibition (ibrutinib). Single-cell RNA sequencing data from SSc and control skin and lung samples (skin: 19 SSc, 20 healthy; lung: 7 SSc, 15 healthy), complemented by spatial transcriptomics analysis of skin (12 SSc, 7 healthy), were integrated to define cellular interactions relevant to disease pathogenesis. Functional studies and bulk RNA sequencing were conducted to dissect the underlying G-MDSC interactions.</p><p><strong>Results: </strong>G-MDSCs were significantly enriched in the circulation and skin of SSc patients, correlating with disease severity. Experimental fibrosis revealed enrichment of G-MDSCs, whereas monocytic MDSCs remained stable. Transcriptomic data revealed a strong interaction between MDSCs and type 2 innate lymphoid cells (ILC2s), promoting a pro-fibrotic environment via IL-13-driven TGFβ, Arginase1 and CCL24. Functional assays confirmed that G-MDSCs promote Tgfb1 expression in ILC2s, further driving tissue fibrosis.</p><p><strong>Conclusion: </strong>These findings explore a so far unknown G-MDSC-ILC2 axis as a driver of fibrosis in SSc. Targeting this interaction may represent a novel therapeutic strategy to mitigate fibrotic disease progression.</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":"148899862","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":"Single-Cell RNA Sequencing of Peripheral Blood Defines Two Immunologic Subtypes of Sjögren's Disease Distinguished by Anti-SSA Antibodies and Aberrant B Cell Populations.","authors":"Geoffrey Urbanski, Kimberly E Taylor, Emily Flynn, Armita Norouzi, Catherine Chu, Brittany Davidson, Arnab Ghosh, Joanne Nititham, Ravi K Patel, Annie W Poon, Gabriela K Fragiadakis, Alexis J Combes, Walter L Eckalbar, Lindsey A Criswell, Chun Jimmie Ye, Caroline H Shiboski","doi":"10.1002/art.70320","DOIUrl":"10.1002/art.70320","url":null,"abstract":"<p><strong>Objective: </strong>Sjögren's disease (SjD) is a heterogeneous autoimmune disorder characterized by substantial clinical and molecular diversity. This heterogeneity raises key questions regarding the existence of distinct pathogenic mechanisms underlying disease subtypes. The objective of this study was to comprehensively characterize peripheral immune cell states associated with SjD and to identify features that could enable better patient stratification for targeted treatments.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing with surface protein profiling on 1.5 million peripheral blood mononuclear cells from 333 participants. Individuals were stratified by SjD diagnosis and anti-SSA status to enable comparative analyses between disease subgroups and controls.</p><p><strong>Results: </strong>Our analysis identified two immunologic endotypes of SjD, with SSA-positive participants exhibiting a dominant and persistent type I interferon signature that was also associated with altered immune cell composition. Transitional B cells were particularly affected, displaying altered developmental states, reduced BCR diversity, shorter CDR3 regions, and increased predicted interactions with activated immune cell populations, findings consistent with perturbations of early B cell selection processes. By contrast, SSA-negative participants with SjD exhibited limited transcriptional differences compared with symptomatic non-SjD controls, highlighting substantial biologic heterogeneity within SjD.</p><p><strong>Conclusion: </strong>These findings support a two-disease model of SjD and highlight transitional B cells as both a key biomarker and a therapeutic target.</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":"148899868","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":"Human Monocytic Models Reveal Genotype-Dependent Inflammatory Programs in VEXAS Syndrome.","authors":"Kana Higashitani, Tatsuma Ban, Yohei Kirino, Go R Sato, Soichiro Adachi, Yuki Iizuka, Kayo Harita, Ayaka Maeda, Osamu Ohara, Hideaki Nakajima, Tomohiko Tamura","doi":"10.1002/art.70332","DOIUrl":"10.1002/art.70332","url":null,"abstract":"<p><strong>Objective: </strong>VEXAS syndrome is a severe X-linked autoinflammatory disorder caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1), with clinical outcomes that vary by UBA1 genotype. We aimed to elucidate genotype-specific inflammatory programs and identify potential therapeutic targets.</p><p><strong>Methods: </strong>We conducted longitudinal deep phenotyping, including whole blood RNA sequencing (RNA-seq) and clinical activity assessment. Peripheral blood samples were analyzed by single-cell RNA-seq. Human monocytic cell lines harboring each major UBA1 mutation (p.Met41Val, p.Met41Thr, or p.Met41Leu) were generated and subjected to transcriptomic and functional analyses.</p><p><strong>Results: </strong>Thirteen patients with VEXAS syndrome contributed a total of 79 RNA-seq samples. Among genes up-regulated in VEXAS syndrome, RNASE1 showed the strongest correlation with longitudinal disease activity (r = 0.70, false discovery rate < 0.05) and was up-regulated in patients' monocytes. In UBA1-mutant monocytic cell lines, genotype-dependent ubiquitination defects were observed in a graded manner (p.Met41Val > p.Met41Thr > p.Met41Leu), even in the absence of exogenous stimuli. These defects were accompanied by unfolded protein response activation, increased pro-inflammatory cytokine production, progressive cell death, and RNASE1 up-regulation, all following the same graded pattern of recapitulating patient genotype-phenotype associations. Transcriptomic analyses demonstrated enrichment of pro-inflammatory, interferon, and necroptosis signatures in more severe genotypes. Notably, inhibition of receptor-interacting protein kinase 3 (RIPK3) markedly attenuated all pathologic features, including RNASE1 up-regulation.</p><p><strong>Conclusion: </strong>Our UBA1-mutant monocytic cell-line models, representing three distinct genotypes, recapitulate genotype-dependent inflammatory phenotypes that can be modulated by RIPK3 inhibition, providing a translational platform for mechanistic investigation and precision therapy development in VEXAS syndrome.</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":"148899849","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":"Optimizing Efficacy to Safety Ratio of Glucocorticoids in Rheumatoid Arthritis Models by Leveraging Peroxisome Proliferator-Activated Nuclear Receptor-α Agonism.","authors":"Lisa L Koorneef, Elisabeth Gilis, Dorien Clarisse, Daria Fijalkowska, Sara Dufour, Julie Coudeneys, Bert Luyckx, Annick Verhee, Jonathan Thommis, Candice Vanden Bussche, Ulf Müller-Ladner, Elena Neumann, Matthias Kerkhofs, Guillaume Planckaert, Simon Devos, Leander Meuris, Dirk Elewaut, Karolien De Bosscher","doi":"10.1002/art.70331","DOIUrl":"10.1002/art.70331","url":null,"abstract":"<p><strong>Objective: </strong>Glucocorticoids remain essential therapies for immune and inflammatory diseases such as rheumatoid arthritis (RA) but are notorious for their metabolic side effects. Given the anti-inflammatory and metabolically favorable actions of peroxisome proliferator-activated nuclear receptor (PPAR) agonists, we investigated whether PPARα agonism could enhance the therapeutic efficacy and/or mitigate the metabolic side effects of glucocorticoids.</p><p><strong>Methods: </strong>We evaluated the effects of the synthetic glucocorticoid dexamethasone and the PPARα agonist GW7647 across four model systems: tumor necrosis factor-α (TNFα)-stimulated L929sA fibroblasts, primary human fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and RA, and collagen-induced arthritis mice.</p><p><strong>Results: </strong>Dexamethasone reduced the inflammatory TNFα response in L929sA cells, which was further potentiated by GW7647. In vivo, dexamethasone induced adiposity and hypertriglyceridemia, which GW7647 counteracted without affecting arthritis severity. In both OA-FLS and RA-FLS, dexamethasone and GW7647 cooperatively regulated metabolic genes expression. Proteomic profiling of TNFα-stimulated human OA-FLS revealed that combined use of dexamethasone and GW suppressed interferon-stimulated proteins. In line herewith, suppression of proinflammatory gene expression upon combined dexamethasone and GW7647 treatment was more outspoken in L929sA co-stimulated with TNFα and interferon-β compared to TNFα alone.</p><p><strong>Conclusion: </strong>GW enhances the anti-inflammatory effects of glucocorticoids in L929sA cells and mitigates metabolic side effects of dexamethasone in vivo, without compromising efficacy. In human OA-FLS and RA-FLS, this combination cooperatively regulates metabolic gene expression. Moreover, PPARα agonism permits to broaden its anti-inflammatory profile to interferon-driven pathways. Because both glucocorticoids and PPAR agonists are already widely used in clinical practice, these findings offer a promising strategy to optimize glucocorticoid-based therapies.</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":"148899808","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":"CD248: Guardian of Synovial Fibroblast Fate.","authors":"Ellen M Gravallese, Kevin Wei","doi":"10.1002/art.70323","DOIUrl":"10.1002/art.70323","url":null,"abstract":"","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":"148899861","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}