Arthritis & Rheumatology最新文献

{"title":"Genetic analysis of asymptomatic antinuclear antibody production","authors":"Mehmet Hocaoglu, Desiré Casares‐Marfil, Amr H. Sawalha","doi":"10.1002/art.43032","DOIUrl":"https://doi.org/10.1002/art.43032","url":null,"abstract":"ObjectiveAntinuclear antibodies (ANA) are detected in up to 14% of the population, and the majority of individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity in the population is limited. In this study, we aimed to perform a genome‐wide association study (GWAS) of asymptomatic ANA positivity in multiple populations.MethodsAsymptomatic ANA positive and negative individuals from the All of Us Research Program were included in this study, selecting those with an ANA test by immunofluorescence and no evidence of autoimmune disease. Imputation was performed and a multi‐population meta‐analysis including approximately 6 million single‐nucleotide polymorphisms (SNPs) was conducted. Genome‐wide SNP based heritability was estimated using the GCTA software. A cumulative genetic risk score for lupus was constructed using previously reported genome‐wide significant loci.Results1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals were included across three genetic populations. The multi‐population meta‐analysis revealed SNPs with a suggestive association (p‐value &lt; 1×10<jats:sup>‐5</jats:sup>) across 8 different loci, but no genome‐wide significant loci were identified. A gene variant upstream of <jats:italic>HLA‐DQB1</jats:italic> (rs17211748, <jats:italic>P</jats:italic> = 1.4×10<jats:sup>‐6</jats:sup>, OR = 0.82, 95% CI 0.76‐0.89) showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Asymptomatic ANA positive individuals did not exhibit increased cumulative genetic risk for lupus compared to ANA negative individuals.ConclusionANA production is not associated with significant genetic risk and is primarily determined by environmental factors.<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/art43032-toc-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"40 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449503","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":"Systemic Sclerosis dermal fibroblast exosomes trigger a Type 1 interferon response in keratinocytes through the TBK/JAK/STAT signalling axis","authors":"Jessica Bryon, Christopher W Wasson, Katja Koeppen, Francesca Chandler, Leon F Willis, Stefano Di Donato, Elliott Klein, Elton Zeqiraj, Rebecca L Ross, Francesco Del Galdo","doi":"10.1002/art.43029","DOIUrl":"https://doi.org/10.1002/art.43029","url":null,"abstract":"BackgroundActivation of Type I IFN response has been shown to correlates with disease activity in systemic sclerosis. It is currently unknown whether the tissue‐specific Type I IFN activation is a consequence of the response observed in blood or rather its source. Exosomes from SSc fibroblasts were recently shown to activate macrophages <jats:italic>in vitro</jats:italic>. Here, we aimed to determine the source of Type I IFN signature in SSc skin biopsies and the potential role of exosomes from SSc dermal fibroblasts in the process.MethodsSkin biopsies were obtained from healthy and SSc patients’ forearms and processed for dermal fibroblasts and keratinocytes. Exosomes were isolated from healthy and SSc dermal fibroblast supernatants by ultracentrifugation and added to human skin keratinocytes. Keratinocyte transcriptome was analysed by RNA‐seq analysis. TANK‐binding kinase (TBK) and JAK were inhibited using a small molecule inhibitor (GSK8612) and Tofacitinib, respectively.ResultsSSc skin biopsies showed highest levels of Type I IFN response in the epidermal layer. RNA‐seq analysis of keratinocytes transcriptome following exposure to dermal fibroblast exosomes showed strong upregulation of IFN signature genes induced by SSc exosomes compared to Healthy control. Inhibition of TBK or JAK activity suppressed the upregulation of the IFN signature induced by SSc exosomes.ConclusionIFN activation of SSc keratinocytes is dependent on their crosstalk with dermal fibroblasts and inducible by extracellular exosomes. Our data indicates that SSc fibroblasts exosomes contributes to theType I IFN activation in SSc skin through activation of pattern recognition receptors upstream of TBK.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"13 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448674","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":"Sigrid R Moe, Øyvind Molberg, Hilde Haukeland, Karoline Lerang","doi":"10.1002/art.43031","DOIUrl":"10.1002/art.43031","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453972","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":"Role of Autoantibodies in Lupus Nephritis: reply.","authors":"Andrea Fava,Catriona A Wagner,Judith A James","doi":"10.1002/art.43033","DOIUrl":"https://doi.org/10.1002/art.43033","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"232 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448075","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":"Role of Autoantibodies in Lupus Nephritis: comment on the article by Fava et al.","authors":"Lingxiang Ran,Rui Zhao,Guangmo Hu","doi":"10.1002/art.43035","DOIUrl":"https://doi.org/10.1002/art.43035","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"68 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448073","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":"JAK Inhibitors vs. Biologic DMARDs: Which is More Effective for Rheumatoid Arthritis Pain?","authors":"Abigail Weiland, Yvonne C. Lee","doi":"10.1002/art.43026","DOIUrl":"https://doi.org/10.1002/art.43026","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"193 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431579","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":"Osteoarthritis: MRI Definitions and Disease Progression","authors":"David T. Felson","doi":"10.1002/art.43022","DOIUrl":"https://doi.org/10.1002/art.43022","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"67 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431580","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":"Weight Reduction and Target Serum Urate Level: A Longitudinal Study of Annual Medical Examination","authors":"Sho Fukui, Masato Okada, Tomohiro Shinozaki, Takahiro Suzuki, Takehiro Nakai, Hiroki Ozawa, Hiromichi Tamaki, Mitsumasa Kishimoto, Hiroshi Hasegawa, Takeaki Matsuda, Javier Marrugo, Sara K Tedeschi, Hyon K Choi, Daniel H. Solomon","doi":"10.1002/art.43027","DOIUrl":"https://doi.org/10.1002/art.43027","url":null,"abstract":"To evaluate associations of weight reduction with serum urate (SU) changes and achieving an SU &lt;6 mg/dl in the real-world setting, outside of specific weight reduction interventions.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"9 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431578","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":"Incorrect about ICD coding for SLE","authors":"Johannes Nossent","doi":"10.1002/art.43025","DOIUrl":"https://doi.org/10.1002/art.43025","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"115 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431434","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":"Enhancing Health Care Affordability: Strategies for Accelerating Biosimilar Uptake","authors":"Dongzhe Hong,&nbsp;Aaron S. Kesselheim","doi":"10.1002/art.43030","DOIUrl":"10.1002/art.43030","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"76 12","pages":"1702-1704"},"PeriodicalIF":11.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431385","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}