Arthritis & Rheumatology最新文献

{"title":"Clinical Images: String of pearls embellishing lupus.","authors":"Sakir Ahmed, Paridhi Vaidh, Mitanjali Sethy, Pankti Ilesh Macwan","doi":"10.1002/art.70328","DOIUrl":"10.1002/art.70328","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":"148899878","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/Endosialin Regulates Synovial Fibroblast State to Control Coupling of Inflammation and Bone Damage in Murine Models of Immune-Mediated Inflammatory Arthritis and Aging.","authors":"Samuel Kemble, Corinna Wehmeyer, James M Brown, Charlotte G Smith, Holly R Adams, Eva Crombie, Ellie Northall, Maryam Imran, Paulynn Chin, Harris R Perlman, Christopher D Buckley, Adam P Croft, Amy J Naylor","doi":"10.1002/art.70327","DOIUrl":"10.1002/art.70327","url":null,"abstract":"<p><strong>Objective: </strong>Synovial fibroblasts directly contribute to inflammation and damage in immune-mediated inflammatory arthritis. CD248/endosialin is expressed by fibroblasts in the synovium, is highly up-regulated during inflammation, and has been proposed as a potential therapeutic target. This study aimed to map the expression of CD248 in disease-associated fibroblast states and to elucidate its role in pathology.</p><p><strong>Methods: </strong>Molecular profiling of stromal cells from healthy and arthritic (K/BxN serum transfer-induced arthritis) wildtype (Cd248^+/+) and Cd248^-/- mice was performed using 3' single-cell RNA sequencing. Arthritis trajectory and severity were assessed in both genotypes by clinical scoring, microcomputed tomography (micro-CT), histology, and flow cytometry of dissociated synovium. Additionally, healthy mice of each genotype were aged to 20 months and hind limbs assessed by micro-CT and histology.</p><p><strong>Results: </strong>Cells expressing high levels of Cd248 also express the \"Pi16\" fibroblast progenitor gene signature. Genetic deletion of Cd248 in mice altered the differentiation trajectory of these progenitors, predisposing them to become destructive lining layer fibroblasts. Consequently, Cd248^-/- arthritic mice showed a phenotype of rapid, extensive bone damage. Unexpectedly, bone erosion and resultant deformity were also observed in aged Cd248^-/- mice in the absence of an inflammatory stimulus.</p><p><strong>Conclusion: </strong>Genetic deletion of Cd248^-/- results in uncoupling of inflammation and damage due to dysregulated fibroblast progenitor differentiation. Our data suggest that the high levels of CD248 expression seen on synovial fibroblasts provides a protective brake that attenuates bone damage by preventing the polarization of emergent fibroblasts toward a destructive phenotype. Therapeutic targeting of this protein may exacerbate disease.</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":"148899877","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":"DNMT3a loss in T cells attenuates experimental arthritis: implications for interpreting human clonal hematopoiesis of indeterminate potential-rheumatoid arthritis associations: comment on the article by Shen et al.","authors":"Qiang Tong","doi":"10.1002/art.70308","DOIUrl":"https://doi.org/10.1002/art.70308","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899880","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":"CASTOR1 Regulates Humoral Immune Responses and Contributes to the Pathogenesis of Systemic Lupus Erythematosus.","authors":"Takeshi Kusuda, Toshihiko Komai, Takahiro Itamiya, Tatsuki Abe, Tomohisa Okamura, Keishi Fujio","doi":"10.1002/art.70314","DOIUrl":"10.1002/art.70314","url":null,"abstract":"<p><strong>Objective: </strong>CASTOR1 senses arginine and regulates mammalian target of rapamycin complex 1 (mTORC1), a central metabolic signaling molecule. This study aimed to elucidate the roles of CASTOR1 in humoral immune responses.</p><p><strong>Methods: </strong>We analyzed human B cell transcriptomes from healthy controls and patients with systemic lupus erythematosus (SLE) via correlation analysis and gene set variation analysis using our database, Immune Cell Gene Expression Atlas from the University of Tokyo. Castor1-deficient and B cell-specific Castor1-deficient mice were used for analyses of serum immunoglobulins and autoantibodies, urinary proteins, renal pathology, gene expression, and flow cytometry in spleen and bone marrow cells. The culture supernatant of splenic B cells was used for immunoglobulin (Ig) analysis.</p><p><strong>Results: </strong>Transcriptomic analysis of bulk RNA sequencing data from various B cell subsets in patients with SLE (n = 136; n = 129 included in the primary analysis) revealed a correlation between CASTOR1 expression and disease activity, with CASTOR1 expression in plasmablasts inversely correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (r = -0.32, P = 0.00031). Castor1-deficient mice exhibited increased plasma cell populations in the spleen and bone marrow, elevated serum IgG levels, production of anti-double-stranded DNA antibodies, and glomerulonephritis with IgG deposits, reflecting SLE-like autoimmunity. Moreover, B cell-specific Castor1-deficient mice showed increased plasma cell counts, elevated serum IgG levels, and glomerulonephritis, indicating that Castor1 might regulate systemic humoral immunity via a B cell-intrinsic mechanism.</p><p><strong>Conclusion: </strong>CASTOR1 plays a regulatory role in humoral immunity and may contribute to the pathogenesis of autoimmune diseases such as SLE, representing a potential therapeutic target.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890440","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":"Early synovial regulatory T cell engagement in posttraumatic osteoarthritis.","authors":"Xueyou Zhang, Mingde Cao, Jianting Li, Bruma Sai-Chuen Fu, Michael Tim-Yun Ong, Patrick Shu-Hang Yung","doi":"10.1002/art.70321","DOIUrl":"https://doi.org/10.1002/art.70321","url":null,"abstract":"<p><strong>Objective: </strong>Posttraumatic osteoarthritis (PTOA) develops despite restoration of joint biomechanics, suggesting that early post-injury biological processes within the synovium shape disease trajectories. We investigated whether synovial regulatory T (T_reg) cells are engaged during the early phase following joint injury and whether experimental enrichment of this compartment is associated with altered local inflammation and PTOA-related pathology.</p><p><strong>Methods: </strong>Using surgically induced destabilization of the medial meniscus (DMM) and a non-invasive anterior cruciate ligament (ACL) rupture model in mice, we characterized temporal dynamics and phenotypes of synovial T_reg cells by high-parameter flow cytometry and integrative single-cell transcriptomic analysis. T_reg cells were preferentially expanded using systemic low-dose IL-2/anti-IL-2 complexes or intraarticular adeno-associated virus-mediated IL-2 delivery. Synovial inflammation, cartilage degeneration, and gait function were assessed.</p><p><strong>Results: </strong>Synovial T_reg cells accumulated rapidly after joint injury in both models, acquired activation- and tissue-adaptation-associated phenotypes distinct from lymphoid T_reg populations, and were associated with local immune-compositional changes. Experimental IL-2-mediated enrichment of the synovial T_reg compartment was accompanied by reduced synovitis, attenuated cartilage pathology, and partial improvement in load-bearing gait parameters.</p><p><strong>Conclusion: </strong>Early synovial T_reg engagement represents a candidate joint-localized immunoregulatory feature of PTOA initiation. Experimental enrichment of this compartment was associated with attenuated PTOA-related features, supporting further investigation of T_reg-specific mechanisms and precisely timed, joint-localized immune modulation.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878578","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":"Clarifying the clinical implications of clonal hematopoiesis in late-onset seropositive rheumatoid arthritis: comment on the article by Zhao et al.","authors":"Weiqi Hu, Xun Zhou, Luxue Wang, Changfeng Hu","doi":"10.1002/art.70214","DOIUrl":"10.1002/art.70214","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"2003-2004"},"PeriodicalIF":9.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Images: Complete Distal Phalanx Resorption in Systemic Sclerosis.","authors":"Ken Yoshida","doi":"10.1002/art.70088","DOIUrl":"10.1002/art.70088","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"2000"},"PeriodicalIF":9.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent IL ‐18 fuels expansion of CD38 + HLA ‐ DR + CD8 + T cells in Still's disease and macrophage activation syndrome","authors":"Greta Rogani, Remco G.A. Erkens, Alejandra Bodelón, Tim R. Mocking, Marein T.M. Putmans, Freya M.C.H. Huijsmans, Lyanne J.P.M. Sijbers, Aafke M. De Ligt, Maurice J.H. Van Haaren, Rianne C. Scholman, Noël M.M. Dautzenberg, Joyce I. Meesters‐Ensing, Martina Rossano, Laura Porretti, Stefan Nierkens, Francesca S. Minoia, Sebastian J. Vastert, Jorg van Loosdregt","doi":"10.1002/art.70319","DOIUrl":"https://doi.org/10.1002/art.70319","url":null,"abstract":"Objective Still's disease (SD) is an autoinflammatory disorder characterized by remarkably high IL‐18 levels. Increasing evidence suggests that adaptive immunity also contributes to its pathogenesis, particularly in refractory courses. Macrophage activation syndrome (MAS), one of SD's most severe complications, is associated with further IL‐18 elevation and expansion of CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells. However, whether and when this population emerges during SD remains unknown. We therefore examined CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells across disease stages. Methods CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells were analyzed longitudinally: at SD‐onset (therapy‐naïve; n=19), during clinically inactive disease (n=15), and prior to or at MAS occurrence (n=12). Spectral flow cytometry and bulk RNA‐sequencing were performed. Correlations with clinical and laboratory parameters were assessed. <jats:italic>In vitro</jats:italic> cytokine stimulations of healthy donor (HD)‐derived PBMCs and CD8 <jats:sup>+</jats:sup> lymphocytes were performed to explore mechanisms driving differentiation of these cells. Results CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells were expanded from SD‐onset and peaked in MAS (median: 4.61% and 31.7%, respectively, versus 0.87% in HD). Transcriptomic profiling of these cells revealed enrichment of activation, cytotoxicity, and proliferation programs, which were confirmed at the protein level. Frequencies correlated with markers of systemic inflammation, T‐cell activation, and serum IL‐18 levels. Sustained IL‐18 stimulation <jats:italic>in vitro</jats:italic> induced robust and persistent expansion of CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> cells, recapitulating key <jats:italic>ex vivo</jats:italic> phenotypic features. Conclusion CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> cells, previously primarily associated with MAS, are detectable early in SD. Persistent IL‐18 exposure promotes their expansion. These findings identify CD38 <jats:sup>+</jats:sup> HLA‐DR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells as a potential mechanistic link between SD and MAS and highlight this subset as a candidate therapeutic target. <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/art70319-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"271 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860867","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":"Reply.","authors":"Kun Zhao, Yash Pershad, Alexander G Bick, Robert W Corty","doi":"10.1002/art.70204","DOIUrl":"10.1002/art.70204","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"2004-2005"},"PeriodicalIF":9.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147808915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inosine-Triphosphate-Pyrophosphatase Activity as a Potential Predictor of Methotrexate Remission in Juvenile Idiopathic Arthritis.","authors":"Sofia Sindici Forgiarini, Marianna Lucafò, Debora Curci, Davide Selvestrel, Valentina Moressa, Sofia Pagarin, Barbara Bellich, Martina Franzin, Alberto Tommasini, Mara L Becker, Laura B Ramsey, Susan D Thompson, Carl D Langefeld, Federica Corba, Edoardo Marrani, Gabriele Simonini, Gabriele Stocco, Giuliana Decorti, Andrea Taddio, Serena Pastore","doi":"10.1002/art.70097","DOIUrl":"10.1002/art.70097","url":null,"abstract":"<p><strong>Objective: </strong>Methotrexate (MTX) is the first-line therapy for juvenile idiopathic arthritis (JIA), but up to 40% of patients do not respond to it. Low inosine triphosphate pyrophosphatase (ITPA) activity has been associated with reduced clinical remission. We investigated the role and underlying mechanisms of ITPA in vitro.</p><p><strong>Methods: </strong>ITPA enzymatic activity was measured by high-performance liquid chromatography with ultraviolet detection in erythrocyte lysates from patients with JIA (enrolled in Trieste, Italy; Florence, Italy; and Kansas City, Missouri) receiving weekly MTX (10-15 mg/m²) for at least 12 months. Remission was evaluated by Wallace et al criteria. ITPA rs1127354, which reduces enzyme activity, was genotyped. Immortalized human hepatocytes were transfected with either an ITPA-containing or empty plasmid to evaluate cytotoxicity (MTT), ADORA_2A expression (quantitative polymerase chain reaction), intracellular cyclic AMP (cAMP) (enzyme-linked immunosorbent assay), PKA-Cα expression (immunoblot), and extracellular adenosine metabolites (liquid chromatography-tandem mass spectrometry).</p><p><strong>Results: </strong>A total of 195 patients with JIA (mean age: 8 years, range: 0-22 years, 74% female participants) were enrolled. Patients reaching remission (48%) had higher ITPA activity than nonresponders during therapy and at treatment onset (meta-analysis: P = 0.0004 and P = 0.007, respectively). Predictive cutoffs for overall and onset measurements were identified: 181.9 and 177.8 nmol of inosine monophosphate per hour. None of the patients with variant ITPA rs1127354 achieved remission (Fisher's exact test P = 0.0063); however, 48% of wild-type patients failed to respond. ITPA-overexpressing cells showed elevated MTX sensitivity, cAMP levels, PKA-Cα expression, and hypoxanthine (all P < 0.05, two-way analysis of variance).</p><p><strong>Conclusion: </strong>ITPA activity is a promising predictive biomarker for MTX response in JIA, outperforming ITPA rs1127354 genotyping. Its predictive value is evident at treatment initiation, supporting its use for personalized treatment. Mechanistically, higher enzyme activity may enhance MTX efficacy through the adenosine/inosine-ADORA_2A pathway.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"1989-1999"},"PeriodicalIF":9.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}