Arthritis & Rheumatology最新文献

{"title":"Reply.","authors":"Jinjian Fu, Xiaomin Yu, Jun Wang, Qing Zhou, Qiong Fu","doi":"10.1002/art.70226","DOIUrl":"10.1002/art.70226","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"2181-2182"},"PeriodicalIF":9.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979683","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":"Extraintestinal Reprogramming of Colon‐Derived CD4+ Intraepithelial Lymphocytes Reveals a Mechanism Underlying the Gut‐Joint Axis","authors":"Sarah M. Danielson, Connor Eck, Sucai Liu, Anna Helena Jonsson, Kristine A. Kuhn","doi":"10.1002/art.70358","DOIUrl":"https://doi.org/10.1002/art.70358","url":null,"abstract":"Objective The gut‐joint axis is a central paradigm in spondyloarthritis, yet the cellular mechanisms linking intestinal and joint immunity remain poorly understood. One potential link is TCRαβ <jats:sup>+</jats:sup> CD4 <jats:sup>+</jats:sup> intraepithelial lymphocytes in the colon (cIELs) that can traffic to extraintestinal tissues, including the joint. Within an inflamed joint, trafficked cIELs display both regulatory and inflammatory capacity. We sought to determine whether this functional identity is determined by an impaired epithelium or shaped by the joint environment. Methods We combined colonoscopy‐guided photoconversion in KikGR mice with single‐cell multiomic profiling and flow cytometry to trace and characterize CD4 <jats:sup>+</jats:sup> cIELs in the spleen and joint‐draining lymph nodes. Intestinal perturbation was induced by dextran sodium sulfate (DSS) and epithelial‐specific major histocompatibility complex class II (MHCII) gene deletion. Results Epithelial‐derived CD4 <jats:sup>+</jats:sup> T cells were enriched for tolerogenic phenotypes, marked by expression of CD73, FR4, and Foxp3. This phenotype persisted despite DSS‐induced intestinal inflammation and was independent of epithelial MHCII expression. However, single cell transcriptomic, epigenetic, and T cell receptor analyses revealed that shared clones undergo tissue‐specific transcriptional reprogramming to more activated states after exiting the epithelium. Conclusions These findings define CD4 <jats:sup>+</jats:sup> cIELs as mobile T cells that retain tolerogenic phenotypes with functional plasticity to a more activated state determined by extraintestinal microenvironments, indicating that the local environment of the joint‐draining lymph nodes, rather than the gut, is important in determining the function of gut‐trafficked CD4 <jats:sup>+</jats:sup> T cells. <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/art70358-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086041","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":"Neutrophil-Driven Inflammation in Pediatric Chronic Recurrent Multifocal Osteomyelitis.","authors":"Nataliia Pavliuchenko, Petr Daněk, Hana Malcová, Rudolf Horváth, Dita Cebecauerová, Tomáš Brdička","doi":"10.1002/art.70356","DOIUrl":"10.1002/art.70356","url":null,"abstract":"<p><strong>Objective: </strong>Chronic recurrent multifocal osteomyelitis (CRMO) is a pediatric autoinflammatory bone disease with poorly defined pathophysiology and limited biomarkers. Murine models implicate neutrophils, neutrophil-derived interleukin-1β, and the adapter protein PSTPIP2, but direct evidence in human CRMO is lacking. This study aims to translate findings from mouse models to human disease by investigating the role of neutrophils and PSTPIP2 in CRMO.</p><p><strong>Methods: </strong>Blood samples from 34 patients with CRMO and 20 controls were analyzed by flow cytometry, biochemical assays, and transcriptomic profiling of purified neutrophils. Patients were evaluated across treatment groups (untreated or treated with nonsteroidal anti-inflammatory drugs, zoledronate, or anti-tumor necrosis factor [anti-TNF] therapy). Neutrophil activation, PSTPIP2 expression, inflammatory gene responses, and correlations with clinical parameters were assessed.</p><p><strong>Results: </strong>CRMO neutrophils displayed chronic activation marked by reduced CD62L expression (P = 0.0016; Mann-Whitney test), which correlated with magnetic resonance imaging lesion burden. PSTPIP2 protein levels were consistently decreased (P = 0.0006) despite elevated messenger RNA expression (P = 0.0005) and absence of coding mutations, suggesting inflammation-associated posttranscriptional regulation. Both neutrophil activation and PSTPIP2 down-regulation normalized in patients receiving anti-TNF therapy. Unlike murine models, IL1B expression and CXCL8 expression were not increased. Transcriptomic profiling (four patients and three controls) identified enrichment of NF-κB signaling and inflammatory and chemotaxis pathways with up-regulation of CCL4, CCL4L2, ATL1, VNN1, H2BC7, and LINC02207 and down-regulation of ISL2. Several transcripts correlated with clinical measures of disease burden.</p><p><strong>Conclusion: </strong>These findings identify neutrophil activation and inflammation-sensitive PSTPIP2 deficiency as central features of human CRMO, suggest chemokines as potential biomarkers, and mechanistically explain why TNF blockade provides clinical benefit.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072897","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":"Journal Club","authors":"","doi":"10.1002/art.70317","DOIUrl":"https://doi.org/10.1002/art.70317","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068583","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":"Dual-Targeting BCMA–CD19 CAR-T Cell Therapy in Systemic Lupus Erythematosus: Single-Cell and Immune Repertoire Analysis Reveals Mechanisms of Immune Reconstitution","authors":"Zhenghao He PhD,&nbsp;Weijia Wang MD,&nbsp;Qianwen Li PhD,&nbsp;Shihao Ding MD,&nbsp;Mingxia Wang MD,&nbsp;Ming Hong PhD","doi":"10.1002/art.70117","DOIUrl":"10.1002/art.70117","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate peripheral immune reconstitution following BCMA–CD19 dual-targeting CAR-T therapy in patients with systemic lupus erythematosus (SLE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing and parallel B cell receptor (BCR) and T cell receptor sequencing were performed on peripheral blood mononuclear cells from five patients with SLE before infusion and after peripheral B cell reconstitution (median 90 days postinfusion). These data were integrated with public datasets from seven patients with SLE treated with CD19 single-targeting CAR-T and three healthy controls for comparative analysis (total N = 15 subjects; 176,182 single cells analyzed).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dual-targeting CAR-T induced marked depletion of B-lineage populations, including plasma-lineage clusters that persisted after CD19 therapy. Specifically, cluster 2 decreased from 10.70% to 2.67% and cluster 3 from 9.55% to 3.12% in the dual-targeting cohort, whereas cluster 3 increased (6.78%–12.19%) in the single-targeting comparator. In B cells, dual targeting produced greater suppression of RIG-I/MDA5 and type I interferon transcriptional programs than single-targeting therapy. BCR repertoires shifted toward an IGHM-dominant (49.83%–89.19%, <i>P</i> &lt; 0.05), naïve-biased profile, with contraction of pre-enriched class-switched clones and restoration of diversity toward healthy-like profiles. Clinical improvement was significant (mean SLE Disease Activity Index decreased from 9.6 to 2.4, <i>P</i> &lt; 0.05), paralleling these molecular changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BCMA–CD19 dual CAR-T therapy was associated with deeper depletion of plasma-lineage compartments and a tendency toward more pronounced reversal of SLE-associated molecular signatures. This exploratory finding suggests a potential advantage of dual targeting in achieving a more comprehensive humoral reset in SLE, which warrants further direct comparative studies to determine clinical superiority.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2110-2123"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359244","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":"Journal Club","authors":"","doi":"10.1002/art.70317","DOIUrl":"https://doi.org/10.1002/art.70317","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068203","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":"Subsets of Patients With Lupus Identified by Gene Expression Profiles Exhibit Differential Clinical Responsiveness to Baricitinib","authors":"Prathyusha Bachali MS,&nbsp;Amrie Grammer PhD,&nbsp;Peter E. Lipsky MD","doi":"10.1002/art.70130","DOIUrl":"10.1002/art.70130","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Baricitinib is a JAK1 inhibitor that showed efficacy in patients with systemic lupus erythematosus (SLE) in a phase 2 study but failed to meet the primary endpoint in phase 3 trials. To understand this discrepancy and identify patients with SLE who are responsive to baricitinib, we conducted baseline and longitudinal transcriptomic analysis in patients enrolled in the phase 2 trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-blood samples from 272 patients with SLE were analyzed. Clinical response was assessed using SLE Responder Index-4 after 24 weeks of placebo or baricitinib (2 or 4 mg daily). Gene expression profiling was conducted using Gene Set Variation Analysis (GSVA) of 32 immune-related gene modules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight distinct molecular endotypes (A–H) were identified from baseline GSVA scores, with progressively increasing immune disturbances. Baseline demographics were similar across endotypes, with modest but significant differences in anti–double-stranded DNA and complement levels but no SLE Disease Activity Index differences. Significant clinical responses to baricitinib were confined to endotypes D and G (<i>P</i> = 0.004 and 0.048 vs placebo, with effect sizes of 41.54% and 31.89%, respectively). Importantly, patient clustering based on clinical features failed to identify treatment-responsive subsets. Endotype G demonstrated the most pronounced treatment-related transcriptional modulation, with dose-dependent suppression of interferon, JAK1/JAK2/TYK2 signaling, immunoproteasome, and inflammatory pathways evident as early as week 2 and sustained through week 24. Transcriptional changes in response to baricitinib were largely confined to clinical responders in endotype G. Feature importance analysis identified the interferon and Treg cell signatures as major predictors of response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Transcriptomic analysis identified subsets of patients with SLE responsive to baricitinib.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2138-2148"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147495018","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: Osteopoikilosis presenting as multiple sclerotic bone lesions.","authors":"Muhammed Aslan, Nurcihan Yavuz Savas, Bunyamin Kisacik","doi":"10.1002/art.70350","DOIUrl":"10.1002/art.70350","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068878","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":"Challenges to Research Integrity in Rheumatology: The Threat of Paper Mills, Fraud, and Click Data Science","authors":"Tony R. Merriman PhD,&nbsp;Tristan Pascart MD, PhD,&nbsp;Maria I. Danila MD, MSc, MSPH","doi":"10.1002/art.70190","DOIUrl":"10.1002/art.70190","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2017-2020"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831287","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":"Ixekizumab With Tirzepatide Achieved Greater Disease Control Than Ixekizumab Alone in Adults With Psoriatic Arthritis and Overweight or Obesity: Results From a Randomized Clinical Trial","authors":"Joseph F. Merola MD, MMSc, FAAD, FACR,&nbsp;Philip Mease MD,&nbsp;Alan Kivitz MD, MACR,&nbsp;Naveed Sattar FMedSci,&nbsp;Laura C. Coates MBChB, PhD,&nbsp;Daniel Aletaha MD, MS, MBA,&nbsp;Cynthia E. Kartman RN,&nbsp;Peter Fischer MD,&nbsp;Luna Sun PhD,&nbsp;Píndaro Martínez-Osuna MD,&nbsp;Andris Kronbergs PhD,&nbsp;Purvi Prajapati PhD,&nbsp;Anabela Cardoso MD,&nbsp;Mark C. Genovese MD,&nbsp;Alexis Ogdie MD, MSCE","doi":"10.1002/art.70134","DOIUrl":"10.1002/art.70134","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Overweight or obesity is prevalent in 72% to 82% of individuals with psoriatic arthritis (PsA). We assessed the efficacy and safety of ixekizumab (IXE) concomitantly administered with tirzepatide (TZP) compared with IXE alone in adult participants with active PsA and overweight with at least one weight-related comorbidity or obesity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;TOGETHER-PsA (ClinicalTrials.gov identifier: NCT06588296) is a phase 3b, randomized, 52-week trial in adults with active PsA and overweight (body mass index [BMI] ≥27 to &lt;30) with at least one weight-related comorbidity or obesity (BMI ≥30) using US-approved doses for IXE and TZP. The primary end point was simultaneous achievement of 50% improvement in American College of Rheumatology response criteria (ACR50) and ≥10% weight reduction at 36 weeks. Key secondary outcomes included ACR50. Additional secondary outcomes and patient-reported outcomes (PROs) were assessed. Safety was assessed as adverse events (AEs), treatment-emergent AEs, and serious AEs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 271 participants were randomized (IXE + TZP, n = 138; IXE, n = 133). The primary end point was achieved with significant improvements in the IXE + TZP arm (31.7%) compared to IXE alone (0.8%) (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Greater improvements in ACR50 were demonstrated in IXE + TZP (33.5%) versus IXE alone (20.4%) (&lt;i&gt;P&lt;/i&gt; = 0.02), with significant early separation at week 4 (nominal &lt;i&gt;P&lt;/i&gt; &lt; 0.05). IXE + TZP demonstrated nominally significant improvements in ACR20 (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), minimal disease activity (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), and absolute Psoriasis Area and Severity Index score (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) compared to IXE alone. IXE + TZP demonstrated significant improvements in PROs, including Health Assessment Questionnaire–Disability Index (∆ −0.2; nominal &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and Functional Assessment of Chronic Illness Therapy–Fatigue (improvement of 3.8; nominal &lt;i&gt;P&lt;/i&gt; &lt; 0.01) compared to IXE alone. Safety profiles were consistent with previous studies for each drug.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Participants with active PsA and complex inflammatory-metabolic disease achieved clinically meaningful improvement of PsA, physical function, weight reduction, and quality of life when treated with IXE + TZP compared to IXE alone, with no new safety concerns.&lt;/p&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2089-2101"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147535752","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}