Arthritis & Rheumatology最新文献

{"title":"Critical role for Transglutaminase 2 in scleroderma skin fibrosis and in the development of dermal sclerosis in a mouse model of scleroderma","authors":"Angela Y.Y. Tam, Korsa Khan, Shiwen Xu, Marianne Bergin, Linghong Huang, Erik Arroyo Colon, Danyi Cheng, Elisabetta AM Verderio, Voon Ong, Christopher P Denton, John Atkinson, Tim S Johnson, David J. Abraham","doi":"10.1002/art.43104","DOIUrl":"https://doi.org/10.1002/art.43104","url":null,"abstract":"Scleroderma is a life-threatening autoimmune disease characterized by inflammation, tissue remodelling, and fibrosis. This study aimed to investigate the expression and function of transglutaminase 2 (TGM2) in scleroderma skin and experimentally-induced dermal fibrosis to determine its potential role and therapeutic implications.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"27 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967904","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":"Immune Aging in Rheumatoid Arthritis","authors":"Cornelia M. Weyand, Jörg J. Goronzy","doi":"10.1002/art.43105","DOIUrl":"https://doi.org/10.1002/art.43105","url":null,"abstract":"Rheumatoid arthritis (RA) is a life-long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self-tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with auto-destructive immunity in affected patients, including the process of immune aging. Patients with RA have a signature of premature immune aging, best understood for CD4⁺ T cells which function as pathogenic effectors in this HLA class II-associated disease. Premature immune aging is present in healthy HLA-DRB1*04⁺ individuals, placing accelerated immune aging prior to joint inflammation. Aging-related molecular abnormalities directly implicated in turning RA CD4⁺ T cells into pro-inflammatory effector cells are linked to malfunction of subcellular organelles, such as mitochondria, lysosomes, lipid droplets and the endoplasmic reticulum. Resulting changes in T cell behavior include cellular hypermobility; tissue invasiveness; unopposed mTORC activation; excessive release of tumor necrosis factor α (TNF); lysosomal failure; clonal expansion and immunogenic cell death. Aged and metabolically reprogrammed T cells in RA patients are accompanied by age-associated B cells (ABC), which specialize in autoantibody production. Clonal hematopoiesis drives myeloid cell aging by producing aged monocytes and hypermetabolic macrophages (Mϕ) that sustain the process of inflammaging. Here, we synthesize insights into the relationship of RA risk and immune aging and discuss mechanisms through which immune aging can cause autoimmunity.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"29 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967903","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":"Air Pollution's Hidden Toll: Risks for Rheumatoid Arthritis and RA-Associated Lung Disease","authors":"S. Ajeganova, J. Sokolove","doi":"10.1002/art.43115","DOIUrl":"https://doi.org/10.1002/art.43115","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"21 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967906","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":"Comment on: 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases","authors":"Julian Segan, Michael Putman, Richard Conway","doi":"10.1002/art.43106","DOIUrl":"https://doi.org/10.1002/art.43106","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"37 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936748","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 to: Limitations in the Real‐World Emulation of the HORIZON Pivotal Fracture Trial","authors":"Elvira D'Andrea, Shirley Wang","doi":"10.1002/art.43103","DOIUrl":"https://doi.org/10.1002/art.43103","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"101 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936680","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":"Avoiding placebo as control treatment in rheumatology trials: can we do better?","authors":"Maarten Boers","doi":"10.1002/art.43107","DOIUrl":"https://doi.org/10.1002/art.43107","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"23 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936602","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":"Limitations in the Real‐World Emulation of the HORIZON Pivotal Fracture Trial","authors":"Peng Shih‐Kuei, Poi Kuo, James Cheng‐Chung Wei","doi":"10.1002/art.43102","DOIUrl":"https://doi.org/10.1002/art.43102","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"56 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936750","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":"Refining research on systemic lupus erythematosus with key considerations: comment on the article by Xing et al.","authors":"Qing Zhou","doi":"10.1002/art.42981","DOIUrl":"10.1002/art.42981","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"116"},"PeriodicalIF":11.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071520","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":"Muscle Tissue Transcriptome of Idiopathic Inflammatory Myopathy Reflects the Muscle Damage Process by Monocytes and Presence of Skin Lesions.","authors":"Shinji Izuka, Natsuka Umezawa, Toshihiko Komai, Yusuke Sugimori, Naoki Kimura, Fumitaka Mizoguchi, Yuichiro Fujieda, Keita Ninagawa, Takeshi Iwasaki, Katsuya Suzuki, Tsutomu Takeuchi, Koichiro Ohmura, Tsuneyo Mimori, Tatsuya Atsumi, Eiryo Kawakami, Akari Suzuki, Yuta Kochi, Kazuhiko Yamamoto, Shinsuke Yasuda, Tomohisa Okamura, Mineto Ota, Keishi Fujio","doi":"10.1002/art.42972","DOIUrl":"10.1002/art.42972","url":null,"abstract":"<p><strong>Objective: </strong>We aim to investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM).</p><p><strong>Methods: </strong>Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl transfer RNA synthetase antibodies in the patients with DM (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach.</p><p><strong>Results: </strong>WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and negative monocytes and myeloid dendritic cells. Notably, patients with DM demonstrated enrichment of complement and interferon-α and γ pathway genes compared with those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and the transforming growth factor-β signaling pathway.</p><p><strong>Conclusion: </strong>Our study highlights a significant involvement of monocytes in muscle damage and delineates pathologic differences among IIM subtypes. DM was characterized by complement and interferon-α and γ signaling, whereas ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"99-106"},"PeriodicalIF":11.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003171","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":"Diversity and Epitope Spreading of Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement.","authors":"Hirohito Kotani, Kazuki M Matsuda, Kei Yamaguchi, Chihiro Ono, Emi Kogo, Koji Ogawa, Yuki Kobayashi, Teruyoshi Hisamoto, Ruriko Kawanabe, Ai Kuzumi, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Naoki Goshima, Shinichi Sato, Ayumi Yoshizaki","doi":"10.1002/art.42975","DOIUrl":"10.1002/art.42975","url":null,"abstract":"<p><strong>Objective: </strong>Epitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti-RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc).</p><p><strong>Methods: </strong>We investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full-length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell-free translation system. Subsequently, we prepared antigen-binding plates and measured autoantibodies in the serum of patients with SSc.</p><p><strong>Results: </strong>Autoantibodies against different RNAP III complex subunits were found in patients who were ARA-positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein-D, a biomarker of interstitial lung disease. However, the extent of disease on high-resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker.</p><p><strong>Conclusion: </strong>Our findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":"67-79"},"PeriodicalIF":11.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102476","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}