Arthritis & Rheumatology最新文献

{"title":"The Missing Link in Joint Homeostasis: Telocytes as Master Regulators of the Synovial Lymphatic System","authors":"Irene Rosa PhD, Eloisa Romano PhD, Mirko Manetti PhD","doi":"10.1002/art.70177","DOIUrl":"10.1002/art.70177","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2007-2010"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663940","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":"Targeting Obesity in Psoriatic Arthritis: Is It Time for a Paradigm Change?","authors":"Lihi Eder MD, PhD, Rebecca Haberman MD, Jose U. Scher MD","doi":"10.1002/art.70258","DOIUrl":"10.1002/art.70258","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2014-2016"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148286898","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":"Telocyte Deletion Associated With Loss of Lymphatic Drainage and Exacerbation of Inflammatory-Erosive Arthritis in Mice","authors":"Yue Peng PhD,&nbsp;H. Mark Kenney MD, PhD,&nbsp;Sean Lydon MS,&nbsp;Karen L. de Mesy Bentley MS,&nbsp;Lianping Xing B.Med, PhD,&nbsp;Benjamin D. Korman MD,&nbsp;Christopher T. Ritchlin MD, MPH,&nbsp;Edward M. Schwarz PhD","doi":"10.1002/art.70131","DOIUrl":"10.1002/art.70131","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Patients with rheumatoid arthritis (RA) have lymphatic defects characterized by loss of collecting lymphatic vessel (cLV) contractions of unknown etiology. To elucidate underlying mechanisms, we generated transgenic mice with lymphatic-specific inducible genetics and studied joint-draining lymphatics in zymosan-induced arthritis (ZIA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We crossed novel <i>Efhd1</i>-CreER^T2 and <i>Myoc</i>-CreER^T2 mice to Ai9 tdTomato (tdT) reporter mice to assess tamoxifen-induced transgene expression via single-cell RNA sequencing, whole-mount immunofluorescent microscopy (WMIFM), and immunohistochemistry. We applied electron and confocal microscopy of popliteal lymphatic vessels (PLVs) to examine α smooth muscle actin positive lymphatic muscle cells, mast cell tryptase–positive mast cells, and CD31⁻/CD34⁺ cells. We crossed <i>Efhd1</i>-CreER^T2 and <i>Myoc</i>-CreER^T2 mice to diphtheria toxin-alphafloxed mice to examine: (1) tamoxifen-induced targeted cell deletion; (2) lymphatic function via near-infrared imaging of injected indocyanine green; and (3) effects on ZIA in the knee via longitudinal ultrasound, micro–computed tomography, and histology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multimodal microscopy discovered the presence of peri-PLV spindle-shaped cells with elongated cytoplasmic extensions physically integrated into mast cells. Gene expression studies confirmed these cells are consistent with telocytes, and WMIFM demonstrated peri-PLV tdT⁺ telocyte networks extending from capillaries in the ankle synovium to cLV near the knee. In vivo telocyte depletion decreased lymphatic drainage and exacerbated synovitis and focal erosions in ZIA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Telocyte networks extend from the synovium into mast cells proximal to joint-draining cLVs, and telocyte loss is associated with synovial lymphatic system (SLS) defects and exacerbated joint pathology from inflammatory-erosive arthritis. Thus, SLS telocytes are a novel drug target for RA, and interventions that maintain telocytes (eg, exercise) may improve lymphatic function.</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":"2050-2062"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465497","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":"TWIST1-Mediated Induction of AEBP1 in Fibroblast-Like Synoviocytes Activates Transforming Growth Factor β Signaling to Drive Angiogenesis and Promote Rheumatoid Arthritis","authors":"Zhenyu Li MD,&nbsp;Minglong Cai MD,&nbsp;Wei Huang MD,&nbsp;Xi Wen MM,&nbsp;Yujing Li MD,&nbsp;Jun Sun PhD,&nbsp;Chen Zhu MD,&nbsp;Chao Yang PhD,&nbsp;Zhu Chen MD","doi":"10.1002/art.70124","DOIUrl":"10.1002/art.70124","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;Aggressive fibroblast-like synoviocytes (FLS) drive synovial hyperplasia, extracellular matrix (ECM) remodeling, and pannus formation in rheumatoid arthritis (RA). However, the pathogenic FLS subpopulations and their upstream regulators remain incompletely defined. This study aimed to (i) identify FLS subpopulation(s) responsible for synovial hyperplasia, ECM remodeling, and pannus development, (ii) elucidate the molecular mechanisms regulating their pathogenic activation, and (iii) explore therapeutic strategies targeting FLS activation and pannus-associated neovascularization in RA.&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;We integrated bulk RNA sequencing, proteomics, and single-cell transcriptomics to identify pathogenic FLS subpopulation(s) in RA synovium. Functional assays were conducted to assess the effects of adipocyte enhancer-binding protein 1 (AEBP1) and periostin (POSTN) expression on FLS activation, ECM remodeling, and angiogenesis. Bioinformatic analyses and cell biologic experiments were adopted to identify the upstream regulator responsible for AEBP1 expression in FLS. We subsequently investigated the pathologic impact of TWIST1–AEBP1–POSTN axis in a collagen-induced arthritis (CIA) mice model.&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;We identified a pathogenic POSTN&lt;sup&gt;+&lt;/sup&gt; FLS subgroup selectively enriched within the sublining layer of synovium that exhibited robust ECM remodeling and fibrogenic features. Mechanistically, we showed that AEBP1 was selectively elevated in these cells, in which it activated transforming growth factor β signaling to drive fibroblast activation, migration, and proliferation. Besides, AEBP1 also induced POSTN expression, which was responsible for neovascularization. Further, inflammatory signalings induced TWIST1 expression, which directly regulated AEBP1 transcription in FLS. Intra-articular modulation of AEBP1 in mice with CIA had opposite effects on synovial hyperplasia, bone erosion, and pannus formation. Moreover, the pharmacological inhibition of TWIST1 by harmine-reduced AEBP1 and POSTN expression, limited the expansion of pathogenic THY1&lt;sup&gt;+&lt;/sup&gt; FLS, and alleviated joint pathology.&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;Our study suggests that POSTN&lt;sup&gt;+&lt;/sup&gt; FLS located in the synovial sublining contribute to RA progression through the TWIST1–AEBP1–POSTN axis. Accordingly, targeting of this axis may offer a novel and effective approach for RA treatment.&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;/p&gt;\u0000 ","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2021-2035"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359215","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":"Unveiling Endotypes in Systemic Lupus Erythematosus Through Multiomic Analysis: Insights Into Cardiovascular and Renal Complications","authors":"Tomás Cerdó PhD,&nbsp;Laurel Woodridge PhD,&nbsp;Sagrario Corrales MSc,&nbsp;Juan Rafael Muñoz-Castañeda PhD,&nbsp;Ana Isabel Torralbo BSc,&nbsp;Anisur Rahman MD, PhD,&nbsp;Filipa Farinha MD, PhD,&nbsp;Rafaela Ortega Castro MD, PhD,&nbsp;Pedro Segui MD,&nbsp;Ismael Sanchez-Pareja MSc,&nbsp;Laura Muñoz-Barrera MSc,&nbsp;Christian Merlo BSc,&nbsp;Desiree Ruiz-Vilchez MSc,&nbsp;M. Carmen Ábalos-Aguilera BSc,&nbsp;Pilar Font MD, PhD,&nbsp;Nuria Barbarroja Puerto PhD,&nbsp;PRECISESADS Clinical Consortium,&nbsp;Marta Alarcón-Riquelme MD, PhD,&nbsp;Alejandro Escudero-Contreras MD, PhD,&nbsp;M. Ángeles Aguirre-Zamorano MD, PhD,&nbsp;Carlos Perez-Sanchez PhD,&nbsp;Elizabeth C. Jury PhD,&nbsp;Chary Lopez-Pedrera PhD","doi":"10.1002/art.70127","DOIUrl":"10.1002/art.70127","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) shows clinical and molecular heterogeneity, and cardiovascular (CV) complications and lupus nephritis (LN) remain leading causes of morbidity and mortality. This study investigated whether omic profiling can reveal molecular endotypes linked to these outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serum from 199 patients with SLE underwent proximity extension assay–based proteomics and targeted nuclear magnetic resonance metabolomics. Unsupervised clustering was performed on proteomic data, followed by integrative multiomic factor analysis, logistic regression, and machine learning models. Cohorts with SLE from the University College London, a subset with expanded Olink Reveal panel and untargeted metabolomics, and in vitro (human umbilical vein endothelial cell and HK2) and ex vivo (rat kidneys) models exposed to patient sera were used for validation and mechanistic exploration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Proteomic clustering identified two molecular subgroups (cluster 1 and cluster 2). Compared with cluster 2, cluster 1 showed damage burden and increased rates of LN (1.8-fold), hypertension (3-fold), dyslipidemia (2-fold), obesity (8-fold), and abnormal C-reactive protein/erythrocyte sedimentation rate (4-fold), consistent with CV risk. A total of 47 inflammatory and organ-damage proteins and multiple metabolites were increased in cluster 1. Neural network models based on metabolites and clinical variables discriminated clusters (area under the curve = 0.77), highlighting citrate and lipoproteins as key features. Multiomic analyses and external cohorts confirmed reproducibility and enrichment in pathways related to leukocyte trafficking, endothelial stress, and nephritis. In vitro, serum from patients with SLE induced NF-κB activation in rat kidneys compared with controls, supporting a proinflammatory effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Multiomic profiling delineates molecular endotypes in SLE, integrating immune, vascular, and metabolic pathways associated with CV risk and LN, supporting their potential for precision risk stratification.</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":"2124-2137"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374151","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":"Stirring Up Plasma Cells in Systemic Lupus Erythematosus","authors":"Georg Schett MD","doi":"10.1002/art.70200","DOIUrl":"10.1002/art.70200","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2011-2013"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733286","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":"Association of Clonal Hematopoiesis With Incident, Late-Onset, Seropositive Rheumatoid Arthritis","authors":"Kun Zhao PhD,&nbsp;Yash Pershad BS,&nbsp;J. Brett Heimlich MD, PhD,&nbsp;Michelle Ormseth MD, MSCI,&nbsp;C. Michael Stein MB, ChB,&nbsp;Brian Sharber MS,&nbsp;Caitlyn Vlasschaert MD, PhD,&nbsp;Alexander G. Bick MD, PhD,&nbsp;Robert W. Corty MD, PhD","doi":"10.1002/art.70133","DOIUrl":"10.1002/art.70133","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Clonal hematopoiesis (CH), defined by acquired driver mutations in hematopoietic stem cells, is associated with many inflammatory diseases of aging. We investigated whether CH and its subtypes, CH of indeterminate potential (CHIP) and mosaic chromosomal alteration (mCA), are associated with incident rheumatoid arthritis (RA) and whether complement modifies these associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CHIP was detected in NIH All of Us, Vanderbilt BioVU, and UK Biobank; mCA was detected in UK Biobank. A harmonized, high-specificity phenotyping algorithm was applied across biobanks to identify participants with seropositive and seronegative RA (SPRA and SNRA). Age-scale survival models assessed the effect of CH on risk of incident RA. Effect modification was tested with interaction models with genetically predicted complement protein levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 612,989 participants, 30,840 had CHIP, 1,535 had incident SPRA, and 1,090 had incident SNRA. CHIP was associated with an increased risk of incident SPRA (pooled hazard ratio [HR] 1.26; confidence interval [CI] 1.03–1.52; <i>P</i> = 2.3 × 10⁻²), driven primarily by <i>DNMT3A</i>-mutated CHIP and late-onset RA (HR 1.45; CI 1.13–1.96; <i>P</i> = 3.6 × 10⁻³) but not SNRA. Autosomal mCA and mosaic loss of chromosome Y (mLOY) were associated with an increased risk of incident SPRA (HR 2.12 and 2.85; CI 1.18–3.8 and 1.57–5.19; <i>P</i> = 1.2 × 10⁻² and 6.1 × 10⁻⁴) but not SNRA. Higher genetically predicted levels of C1r and C1s attenuated the CHIP–SPRA association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Age-related CH, including <i>DNMT3A</i>-CHIP, autosomal mCA, and mLOY, are risk factors for incident SPRA but not SNRA, supporting a genotype- and serostatus-specific link between somatic mutation and RA, with the classical complement pathway as a potential modifier.</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":"2063-2073"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471618","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":"Functional Impact of Structural Damage in Psoriatic Arthritis: Insights from a Prospective Cohort Study","authors":"Pankti Mehta MBBS, MD, DM,&nbsp;Shangyi Gao BSc, MSc,&nbsp;Virginia Carrizo Abarza MD,&nbsp;Fadi Kharouf MD,&nbsp;Daniel Pereira BSc,&nbsp;Richard J. Cook BSc, MMath, PhD,&nbsp;Dafna D. Gladman MD, FRCPC, OC,&nbsp;Vinod Chandran MBBS, MD, DM, PhD,&nbsp;Denis Poddubnyy MD, PhD, MSc","doi":"10.1002/art.70145","DOIUrl":"10.1002/art.70145","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To examine the association between radiographic structural damage and physical function (PF) in psoriatic arthritis (PsA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were analyzed from a large longitudinal PsA cohort. PF was measured using the Health Assessment Questionnaire (HAQ, 0–3) and Short Form-36 PF subscale (SF-36, 0–100); radiographic joint damage was measured using the modified Steinbrocker score (mSS, 0–168). Associations between PF and mSS were analyzed using linear mixed models. We also evaluated the impact of the presence of any damaged joint (grade 2–4), joint damage by individual grades, and the number of damaged joints (grade 2–4) per patient on PF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 1,177 patients (mean ± SD age 44.61 ± 12.76 years; 55.8% men), baseline mSS was 2 (interquartile range [IQR] 0–8.5), HAQ was 0.62 (IQR 0.12–1.12), and SF-36 PF was 60 (IQR 35–85). Higher mSS was significantly associated with worse SF-36 PF (β = −0.10; 95% confidence interval [CI] −0.15 to −0.05) and HAQ (β = 0.003; 95% CI 0.002 to 0.004) after controlling for swollen joint count, sex, and disease duration. The number of damaged joints was associated with worse SF-36 PF (β = −0.23; 95% CI −0.38 to −0.08) and HAQ (β = 0.005; 95% CI 0.002 to 0.009). The presence of a damaged joint (grade 2–4) alone did not impact PF. However, the presence of a joint with grade 4 destruction was associated with substantially worse SF-36 PF (β = −3.04; 95% CI −5.93 to −0.15) and HAQ (β = 0.09; 95% CI 0.03 to 0.15). Increasing counts of grade 4 joints demonstrated a strong dose response with SF-36 PF (β = −0.54; 95% CI −0.81 to −0.26) and HAQ (β = 0.01; 95% CI 0.01 to 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Radiographic structural damage, particularly severe joint destruction, is independently associated with impaired PF in PsA, highlighting the importance of early detection and prevention of damage.</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":"2102-2109"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478773","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":"Plasma Proteomics Identifies Molecular Signatures and Biomarkers Associated With High Structural Damage in Ankylosing Spondylitis.","authors":"Tiantian Sun, Wanlin Liu, Kun Yang, Xiaohan Xu, Yu Wang, Xinning Qu, Yifan Gong, Wenya Zhang, Jie Ma, Hongxiao Liu","doi":"10.1002/art.70353","DOIUrl":"10.1002/art.70353","url":null,"abstract":"<p><strong>Objective: </strong>Pathologic bone formation in ankylosing spondylitis (AS) is not fully reflected by systemic inflammation, limiting the utility of markers of inflammation for structural damage assessment. This study aimed to identify plasma protein signatures associated with structural damage severity in AS.</p><p><strong>Methods: </strong>Deep plasma proteomics was conducted in a prospective 88-participant discovery cohort comprising 25 and 31 patients with high and low structural damage, respectively, stratified by the Spondyloarthritis Research Consortium of Canada sacroiliac joint structural score and 32 normal controls. Age- and sex-adjusted differential expression analysis, weighted gene coexpression network analysis (WGCNA), and integrated machine learning were used to characterize damage-associated molecular programs and prioritize biomarkers. Five candidate proteins were validated by enzyme-linked immunosorbent assay in an independent 88-participant cohort (32 high, 32 low, and 24 normal controls).</p><p><strong>Results: </strong>Proteomic profiling identified 536 differentially expressed proteins between the high structural damage group and normal controls. WGCNA revealed a structural-damage-associated module, enriched in platelet activation and cell-matrix adhesion, together with an AS-associated reduction in a module related to RNA processing and translation. Integrated analysis prioritized a five-protein signature comprising ITGA2B, HSPG2, ITGB1, EPHB2, and SAA2. The combined model achieved an area under the curve (AUC) of 0.917 in the validation cohort and significantly outperformed individual biomarkers (AUCs 0.732-0.819; all Holm-adjusted P < 0.05).</p><p><strong>Conclusion: </strong>This study supports a dual-pathway model in which SAA2-marked systemic inflammation and ITGA2B-associated platelet-extracellular matrix remodeling appear partially dissociated yet remain biologically interconnected in AS. The validated five-protein panel provides a noninvasive tool for identifying patients with current high structural damage that complements imaging-based assessment by capturing biologic heterogeneity.</p>","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":"149068842","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 Rare RIPK3 Variant Enhances Necroptosis and Promotes Inflammation in a Still Disease–Like Autoinflammatory Syndrome","authors":"Longfang Chen MD,&nbsp;Qihua Dai MD,&nbsp;Yu Xiao MD,&nbsp;Jialin Dai MD,&nbsp;Mengyan Wang MD,&nbsp;Yuning Ma MD,&nbsp;Yujie Shen MD,&nbsp;Zhimo Xu MD,&nbsp;Jianfen Meng MD,&nbsp;Xia Chen MD,&nbsp;Da Yi MD,&nbsp;Yue Sun PhD,&nbsp;Hui Shi MD,&nbsp;Honglei Liu MD,&nbsp;Xiaobing Cheng MD,&nbsp;Yutong Su MD,&nbsp;Junna Ye MD,&nbsp;Huihui Chi MD,&nbsp;Zhuochao Zhou MD,&nbsp;Tingting Liu MD,&nbsp;Jialin Teng MD,&nbsp;Chengde Yang MD,&nbsp;Jinchao Jia MD,&nbsp;Qiongyi Hu MD","doi":"10.1002/art.70146","DOIUrl":"10.1002/art.70146","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Still disease represents a prototypical polygenic systemic autoinflammatory disease, characterized by recurrent systemic inflammation and dysregulation of innate immunity. Despite extensive clinical characterization, familial clustering Still disease remains unreported. This study investigates a novel variant underlying a distinct Still disease–like autoinflammatory syndrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-exome sequencing was performed in a three-generation family with three affected individuals. Functional analyses were conducted to assess the impact of the receptor-interacting protein kinase 3 (<i>RIPK3</i>) p.Q134K variant on kinase activity, necroptosis, and inflammatory signaling. Transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) and in vitro cytokine assays were used to characterize inflammatory responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A heterozygous <i>RIPK3</i> p.Q134K variant was identified in all affected individuals. Functional analyses demonstrated that this variant exhibits gain-of-function activity, characterized by enhanced RIPK3 kinase activity and increased RIPK3 self-association, which in turn promote mixed-lineage kinase domain-like protein phosphorylation and necroptosis. RNA sequencing of PBMCs from one patient revealed marked up-regulation of NF-κB and MAPK signaling pathways and elevated expression of interleukin-6, and tumor necrosis factor-α, which was effectively suppressed by pharmacologic inhibition of RIPK3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study describes a familial Still disease–like autoinflammatory syndrome caused by a gain-of-function <i>RIPK3</i> variant. Our findings establish aberrant RIPK3 activation as a driver of autoinflammation and expand the spectrum of human RIPK3-associated diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2149-2159"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478776","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}