Arthritis & Rheumatology最新文献

{"title":"Reply to comments on \"Association of thigh intramuscular fat infiltration with incident knee and hip osteoarthritis: a longitudinal cohort study\".","authors":"Qianlin Weng,Ting Jiang,Tuo Yang,Chao Zeng","doi":"10.1002/art.43257","DOIUrl":"https://doi.org/10.1002/art.43257","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"20 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122135","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":"Activin A-activated ALK4 induces pathogenic Th17 involved endothelial–mesenchymal transition in systemic lupus erythematosus-associated pulmonary arterial hypertension","authors":"Shuliang Jing, Junyan Qian, Hongjie Ying, Pei Mao, Mingxin Yao, Zhihong Wu, Harm J Bogaard, Lie Wang, Mengtao Li, Jun Yang","doi":"10.1002/art.43235","DOIUrl":"https://doi.org/10.1002/art.43235","url":null,"abstract":"Autoimmune diseases, such as systemic lupus erythematosus (SLE), are associated with pulmonary arterial hypertension (PAH), a condition that can lead to heart failure. However, whether T cells also contribute to the occurrence of PAH in SLE, has not been clarified. The objective of this study was to elucidate the role of Activin A and activated receptor signaling in SLE-PAH.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"235 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104170","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 importance of considering the gout flare: let's learn to walk and chew gum at the same time in gout clinical trial design.","authors":"Lisa K Stamp,Martin A Kennedy,Nicola Dalbeth","doi":"10.1002/art.43233","DOIUrl":"https://doi.org/10.1002/art.43233","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"131 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103627","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":"Mucosal-associated invariant T cells in rheumatic diseases.","authors":"Manon Lesturgie-Talarek,Virginie Gonzalez,Lucie Beaudoin,Noémie Sénot,Corinne Miceli-Richard,Yannick Allanore,Agnès Lehuen,Jerôme Avouac","doi":"10.1002/art.43242","DOIUrl":"https://doi.org/10.1002/art.43242","url":null,"abstract":"Mucosal-associated invariant T (MAIT) cells are innate-like T cells defined by their semi-invariant T cell receptor (TCR) and restriction by the MHC class I-related molecule (MR1). These cells are primarily activated by microbial-derived metabolites presented by MR1 or by cytokines. Upon activation, MAIT cells rapidly produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-17, and secrete cytotoxic molecules such as granzyme B. Due to their ability to interact with microbiota and accumulate in inflamed tissues, MAIT cells have attracted great interest in autoimmune and inflammatory diseases. In this review, we summarize recent findings on MAIT cells in major rheumatic diseases, including rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren syndrome, and dermatomyositis. Circulating MAIT cells frequency is reduced in these diseases. Interestingly, the residual MAIT cells exhibit an activated profile and increased cytokine-producing capacity in some conditions. Moreover, an enrichment of MAIT cells in inflamed tissues is described in rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, and primary Sjögren syndrome. This pattern suggests that MAIT cells may migrate from the circulation to inflamed tissues, contributing to local immune responses. Furthermore, they have been shown to play a critical role in disease progression in two mouse models. All these findings suggest an involvement of MAIT cells in inflammatory rheumatologic diseases and their potential therapeutic target.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"153 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103617","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":"FGL-1 Modulates Inter-Organ Communication by Controlling T Cell Homeostasis during the Onset of Sjögren's Disease.","authors":"Kunihiro Otsuka,Aya Ushio,Ruka Nagao,Shigefumi Matsuzawa,Rieko Arakaki,Kazuki Fukuta,Yasuhiro Mouri,Takaaki Tsunematsu,Naozumi Ishimaru","doi":"10.1002/art.43236","DOIUrl":"https://doi.org/10.1002/art.43236","url":null,"abstract":"OBJECTIVEAutoimmunity occurs due to the tactics between pathogenic and regulatory factors in systemic organs. Although inter-organ communication has been demonstrated in various diseases, the effects of the crosstalk between the immune system and other organs on autoimmune disease is unknown.METHODSWe analyzed the influence of inter-organ communication on the cellular or molecular mechanism of autoimmunity using a mouse model of primary Sjögren's disease (pSjD) and patients with pSjD by integrative genomic, bioinformatics, pathological, and immunological analyses.RESULTSFibrinogen-like protein-1 (FGL-1) was identified as a potent factor for inter-organ communication between the liver and immune system in pSjD model mice. The production of FGL-1 of the liver is induced by IL-6 from CD4+ T cells in these mice. The onset of autoimmune lesions in Fgl1-deficient pSjD model mice was earlier than that in the WT-pSjD model mice. FGL-1 produced in the liver regulates naïve/memory T cell homeostasis. Further, FGL-1 was significantly upregulated in patients with pSjD compared to the controls. Moreover, its concentration was closely related to the serum IL-6 levels in patients with pSjD.CONCLUSIONFGL-1 plays a key role in the onset of autoimmunity by suppressing T cell activation in pSjD. Our results will facilitate the development of novel diagnostic or therapeutic strategies targeting the inter-organ communication for autoimmune diseases.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"55 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103564","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 Historical Perspective on Approaches to Understanding the Genetics of Systemic Lupus Erythematosus.","authors":"S Louis Bridges,Betty P Tsao,Peter K Gregersen","doi":"10.1002/art.43247","DOIUrl":"https://doi.org/10.1002/art.43247","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"79 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087550","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":"HLA class I-downregulated senescent epidermal basal cells orchestrate skin pathology in cutaneous lupus erythematosus.","authors":"Sena Yamamoto,Yuki Saito,Tsukasa Sato,Seina Nakano,Dain Kasseki,Ayaka Nagao,Norihiro Miura,Kentaro Nagaoka,Arisa Kita,Maki Miyajima,Shogo Ijima,Koji Taniguchi,Atsushi Niida,Takako S Chikenji","doi":"10.1002/art.43244","DOIUrl":"https://doi.org/10.1002/art.43244","url":null,"abstract":"OBJECTIVETo investigate the role of senescent epidermal basal cells in cutaneous lupus erythematosus (CLE) pathogenesis using skin samples from patients with CLE and a mouse model of systemic lupus erythematosus (SLE).METHODSCellular senescence profiling utilized datasets from the NCBI Gene Expression Omnibus database and Accelerating Medicines Partnership® (AMP®) Phase 1-Metro. Gene array data from GSE184989 (CLE: n = 68, control: n = 4), single-cell RNA sequencing data from GSE186476 (CLE: n = 7, control: n = 14), and AMP® Phase 1-Metro (SLE: n = 17) were utilized. In vitro experiments further examined the expression of p21WAF1/CIP1, type I interferon (IFN), human leukocyte antigen class I (HLA-I), and epidermal growth factor receptor (EGFR) signalling. Pharmacological clearance of senescent cells was performed using the senolytic drug fisetin in the SLE mouse model.RESULTSp21WAF1/CIP1-high senescent epidermal basal cells in patients with CLE exhibit high type I IFN expression. These cells enhance IFN signalling in surrounding normal epidermal basal cells, leading to increased HLA-I expression. In contrast, senescent epidermal cells upregulate EGFR signalling, which downregulates HLA-I expression, allowing them to evade immune surveillance. This heterogeneity of HLA-I expression promotes CD8-positive T-mediated toxicity against normal epidermal basal cells, resulting in their apoptosis. Pharmacological clearance of senescent epidermal basal cells improved SLE-like skin lesions.CONCLUSIONSenescent cells create a microenvironment that directs cytotoxic T-cell-mediated responses against normal epidermis in CLE, contributing to disease pathology. Targeting senescent cells and their signalling pathways may offer novel therapeutic strategies for CLE and SLE skin lesions.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"132 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087552","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":"Precision Medicine in Pediatric Autoimmunity: Leniolisib Treatment of Childhood-Onset Lupus Nephritis Due to Activated PI3K-Delta Syndrome (APDS).","authors":"Jonathan P Lim,Mansooreh Ahmadian,Hongyu Du,Christian Rickert,Tusharkanti Ghosh,Fuyong Xing,Angela Minic,Sara A Johnson,Jason P Weinman,Nicholas Willard,Clara Lin,Jennifer C Cooper,Melisha Hanna,Vijaya Knight,Debashis Ghosh,Kimberly R Jordan,Elena Wy Hsieh","doi":"10.1002/art.43254","DOIUrl":"https://doi.org/10.1002/art.43254","url":null,"abstract":"OBJECTIVETo investigate the mechanistic underpinnings and treatment response of lupus nephritis (LN) in activated PI3K-delta syndrome type 1 (APDS1) using pathway-specific therapy and advanced spatial proteomics.METHODWe conducted mechanistic investigation of refractory class V LN in an 18-year-old female with genetically confirmed APDS1 (PIK3CD c.3061G>A, p.E1021K mutation). Response to leniolisib, a selective PI3Kδ inhibitor, was evaluated through clinical parameters and flow cytometry of peripheral blood lymphocytes. Kidney tissue immune architecture was characterized using Multiplexed Ion Beam Imaging Time-of-Flight Spectrometry (MIBI-TOF), comparing the APDS1-LN tissue signature with 12 childhood-onset LN patients (cLN) and 5 healthy controls (HC).RESULTSLeniolisib treatment normalized hyperactive PI3Kδ signaling, resulting in significant improvements in proteinuria, complement levels, and peripheral edema after failing three years of conventional immunosuppressives. MIBI-TOF spatial proteomics revealed a distinct tissue-specific immunopathology with significantly increased proportions of CD8+ T cells (21.6% in APDS1 vs. 12.0% in typical LN, p=0.0410) and M1 macrophages (42.0% in APDS1 vs. 9.0% in typical LN, p=0.1445) clustering around glomeruli with immune complex deposition. This immune signature aligns with the constitutively active PI3Kδ pathway's effect on lymphocyte exhaustion and inflammatory phenotype.CONCLUSIONThis investigation advances rheumatology by demonstrating that APDS1-associated LN displays a specific tissue immune signature and responds to targeted inhibition of the causative molecular pathway. Our findings provide mechanistic insights into genetic drivers of autoimmunity and support pathway-specific therapeutic approaches for refractory autoimmune manifestations in primary immunodeficiencies.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"16 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087553","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":"Hand swelling and other non-Raynaud's symptoms as the initial presentation of systemic sclerosis: prevalence and clinical associations in two U.S. cohorts.","authors":"Iqtidar Hanif,Shervin Assassi,Maureen D Mayes,Zsuzsanna H McMahan,Meng Zhang,Julio Charles,John M VanBuren,Jessica S Alvey,Kimia Ghaffari,Elana J Bernstein,Flavia V Castelino,Lorinda Chung,Luke Evnin,Tracy M Frech,Jessica K Gordon,Faye N Hant,Laura K Hummers,Dinesh Khanna,Kimberly S Lakin,Dorota Lebiedz-Odrobina,Yiming Luo,Ashima Makol,Jerry A Molitor,Duncan F Moore,Carrie Richardson,Nora Sandorfi,Ami A Shah,Ankoor Shah,Victoria K Shanmugam,Virginia D Steen,Elizabeth R Volkmann,Carleigh Zahn,Brian Skaug","doi":"10.1002/art.43237","DOIUrl":"https://doi.org/10.1002/art.43237","url":null,"abstract":"OBJECTIVERaynaud's phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.METHODSAll patient data in the GENISOS and CONQUER cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.RESULTS194/439 (44.2%), and 292/938 (31.1%) patients in GENISOS and CONQUER, respectively, had a non-RP initial symptom, most commonly puffy fingers/hands. Black patients had a non-RP symptom prior to RP more commonly than other race and ethnicity categories. Non-RP first patients were more likely than RP first patients to have diffuse cutaneous involvement and joint contractures at enrollment and had a higher prevalence of RNA Polymerase III antibody positivity.CONCLUSIONIn two large U.S. cohorts, >30% of patients began to manifest SSc with puffy fingers/hands or other symptoms, without the \"warning sign\" of RP as their initial symptom. These patients presented with more severe skin and musculoskeletal disease on average, highlighting the importance of early recognition. The most common autoantibody associated with this presentation was RNA Polymerase III. These results should be considered in efforts to recognize SSc in its earliest stages. Puffy fingers/hands, even in the absence of RP, should prompt consideration of early SSc and testing for ANA and SSc-associated autoantibodies including RNA Polymerase III.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"128 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087555","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 thigh intramuscular fat infiltration with incident knee and hip osteoarthritis: a longitudinal cohort study: Comment on the article Weng Q et al.","authors":"Duygu Tecer,Sedat Yilmaz","doi":"10.1002/art.43246","DOIUrl":"https://doi.org/10.1002/art.43246","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"58 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087546","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}