Catherine Zhu, Younghun Han, Jinyoung Byun, Xiangjun Xiao, Simon Rothwell, Frederick W. Miller, Ingrid E. Lundberg, Peter K. Gregersen, Jiri Vencovsky, Vikram R. Shaw, Neil McHugh, Vidya Limaye, Albert Selva-O'Callaghan, Michael G. Hanna, Pedro M. Machado, Lauren M. Pachman, Ann M. Reed, Lisa G. Rider, Øyvind Molberg, Olivier Benveniste, Timothy Radstake, Andrea Doria, Jan L. De Bleecker, Boel De Paepe, Britta Maurer, William E. Ollier, Leonid Padyukov, Lucy R. Wedderburn, Hector Chinoy, Janine A. Lamb, Christopher I. Amos
Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.
{"title":"Meta-analyses uncover the genetic architecture of Idiopathic Inflammatory Myopathies","authors":"Catherine Zhu, Younghun Han, Jinyoung Byun, Xiangjun Xiao, Simon Rothwell, Frederick W. Miller, Ingrid E. Lundberg, Peter K. Gregersen, Jiri Vencovsky, Vikram R. Shaw, Neil McHugh, Vidya Limaye, Albert Selva-O'Callaghan, Michael G. Hanna, Pedro M. Machado, Lauren M. Pachman, Ann M. Reed, Lisa G. Rider, Øyvind Molberg, Olivier Benveniste, Timothy Radstake, Andrea Doria, Jan L. De Bleecker, Boel De Paepe, Britta Maurer, William E. Ollier, Leonid Padyukov, Lucy R. Wedderburn, Hector Chinoy, Janine A. Lamb, Christopher I. Amos","doi":"10.1002/art.43088","DOIUrl":"https://doi.org/10.1002/art.43088","url":null,"abstract":"Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"34 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825162","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}
Devin Driscoll, Navya George, Christine Peloquin, S. Reza Jafarzadeh, Jean W. Liew, Maureen Dubreuil
People with axial spondyloarthritis (axSpA) have increased fracture risk relative to the general population, possibly related to chronic inflammation. We assessed the impact of treatment with tumor necrosis factor inhibitors (TNFi) and non-biologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in axSpA, relative to nonsteroidal anti-inflammatory drugs (NSAIDs).
{"title":"Association of Therapies for Axial Spondyloarthritis on the Risk of Hip and Spine Fractures","authors":"Devin Driscoll, Navya George, Christine Peloquin, S. Reza Jafarzadeh, Jean W. Liew, Maureen Dubreuil","doi":"10.1002/art.43082","DOIUrl":"https://doi.org/10.1002/art.43082","url":null,"abstract":"People with axial spondyloarthritis (axSpA) have increased fracture risk relative to the general population, possibly related to chronic inflammation. We assessed the impact of treatment with tumor necrosis factor inhibitors (TNFi) and non-biologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in axSpA, relative to nonsteroidal anti-inflammatory drugs (NSAIDs).","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"29 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825165","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}
Edoardo Cipolletta, Laila J. Tata, Abhishek Abhishek
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{"title":"Reply to: Short-term risk of cardiovascular events in people newly diagnosed with gout: comment on the article by Cipolletta et al.","authors":"Edoardo Cipolletta, Laila J. Tata, Abhishek Abhishek","doi":"10.1002/art.43092","DOIUrl":"https://doi.org/10.1002/art.43092","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"120 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825161","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}
Yiming Luo, Atlas Khan, Lili Liu, Cue Hyunkyu Lee, Gabriel J Perreault, Sydney F Pomenti, Pravitt Gourh, Krzysztof Kiryluk, Elana J Bernstein
ObjectiveAn increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross‐phenotype GWAS meta‐analysis.MethodsWe performed cross‐phenotype GWAS meta‐analysis and Bayesian colocalization analysis for SSc and PBC. We performed both genome‐wide and locus‐based analysis, including tissue and pathway enrichment analyses, fine‐mapping, Bayesian colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome‐wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci.ResultsWe detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 x 10‐6). In the cross‐phenotype GWAS meta‐analysis, we identified 44 non‐HLA loci that reached genome‐wide significance (p < 5 x 10‐8). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans‐pQTLs of multiple plasma proteins involved in B cell function.ConclusionOur study supports a strong shared genetic susceptibility between SSc and PBC. Through cross‐phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.
{"title":"Cross‐Phenotype Genome‐Wide Association Study Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis","authors":"Yiming Luo, Atlas Khan, Lili Liu, Cue Hyunkyu Lee, Gabriel J Perreault, Sydney F Pomenti, Pravitt Gourh, Krzysztof Kiryluk, Elana J Bernstein","doi":"10.1002/art.43081","DOIUrl":"https://doi.org/10.1002/art.43081","url":null,"abstract":"ObjectiveAn increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross‐phenotype GWAS meta‐analysis.MethodsWe performed cross‐phenotype GWAS meta‐analysis and Bayesian colocalization analysis for SSc and PBC. We performed both genome‐wide and locus‐based analysis, including tissue and pathway enrichment analyses, fine‐mapping, Bayesian colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome‐wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci.ResultsWe detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 x 10<jats:sup>‐6</jats:sup>). In the cross‐phenotype GWAS meta‐analysis, we identified 44 non‐HLA loci that reached genome‐wide significance (p < 5 x 10<jats:sup>‐8</jats:sup>). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized <jats:italic>CD40</jats:italic>, <jats:italic>ERAP1</jats:italic>, <jats:italic>PLD4</jats:italic>, <jats:italic>SPPL3,</jats:italic> and <jats:italic>CCDC113</jats:italic> as novel candidate causal genes. The <jats:italic>CD40</jats:italic> risk locus colocalized with trans‐pQTLs of multiple plasma proteins involved in B cell function.ConclusionOur study supports a strong shared genetic susceptibility between SSc and PBC. Through cross‐phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"47 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825169","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}
Anne-Priscille Trouvin, Arielle Simunek, Joël Coste, Terkia Medkour, Alice Combier, Lucile Poiroux, François Vidal, Sandrine Carvès, Didier Bouhassira, Serge Perrot
In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of bDMARDs. The objective of the RAPID (Rheumatism Pain Inhibitory Descending pathways) study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a TNF inhibitor. (TNFi)
{"title":"Changes in descending pain modulation during anti-TNF therapy. A prospective study in rheumatoid arthritis and spondyloarthritis","authors":"Anne-Priscille Trouvin, Arielle Simunek, Joël Coste, Terkia Medkour, Alice Combier, Lucile Poiroux, François Vidal, Sandrine Carvès, Didier Bouhassira, Serge Perrot","doi":"10.1002/art.43084","DOIUrl":"https://doi.org/10.1002/art.43084","url":null,"abstract":"In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of bDMARDs. The objective of the RAPID (Rheumatism Pain Inhibitory Descending pathways) study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a TNF inhibitor. (TNFi)","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"46 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825164","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":"Response to the Comment by Guo et al. on Enhancing Knee Osteoarthritis Prediction","authors":"Shengfa Li, Changhai Ding","doi":"10.1002/art.43085","DOIUrl":"https://doi.org/10.1002/art.43085","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":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825167","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 Knee Osteoarthritis Prediction: Comment on the Article by Li et al","authors":"Qin Guo, Hui Li, Chengshan Guo","doi":"10.1002/art.43087","DOIUrl":"https://doi.org/10.1002/art.43087","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":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825163","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":"Revisiting the Synovium as a Structural Correlate of Pain in Osteoarthritis","authors":"Rachel E. Miller, Richard F. Loeser","doi":"10.1002/art.43086","DOIUrl":"https://doi.org/10.1002/art.43086","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"3 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825166","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}
Johanna M. Kroese, Bernd W. Brandt, Mark J. Buijs, Wim Crielaard, Frank Lobbezoo, Bruno G. Loos, Laurette van Boheemen, Dirkjan van Schaardenburg, Egija Zaura, Catherine M.C. Volgenant
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{"title":"The oral microbiota in persons at risk for rheumatoid arthritis: follow-up data","authors":"Johanna M. Kroese, Bernd W. Brandt, Mark J. Buijs, Wim Crielaard, Frank Lobbezoo, Bruno G. Loos, Laurette van Boheemen, Dirkjan van Schaardenburg, Egija Zaura, Catherine M.C. Volgenant","doi":"10.1002/art.43090","DOIUrl":"https://doi.org/10.1002/art.43090","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"42 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825160","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}
Martina Uzzo, Helmut Schumacher, Juergen Steffgen, Simone Deutschel, David Jayne, Ingeborg Bajema
A phase II trial tested different doses of the anti-CD40 monoclonal antibody BI655064 as add-on therapy to the standard of care in class III or IV Lupus Nephritis (LN) patients with active disease. A post-hoc analysis showed a potential benefit of the higher tested doses (180mg/240mg) versus low dose (120mg)/placebo. We investigated whether the treatment effect of BI655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well-known role in LN pathogenesis.
{"title":"Outcome of lupus nephritis patients treated with an anti-CD40 monoclonal antibody according to kidney biopsy features","authors":"Martina Uzzo, Helmut Schumacher, Juergen Steffgen, Simone Deutschel, David Jayne, Ingeborg Bajema","doi":"10.1002/art.43076","DOIUrl":"https://doi.org/10.1002/art.43076","url":null,"abstract":"A phase II trial tested different doses of the anti-CD40 monoclonal antibody BI655064 as add-on therapy to the standard of care in class III or IV Lupus Nephritis (LN) patients with active disease. A post-hoc analysis showed a potential benefit of the higher tested doses (180mg/240mg) versus low dose (120mg)/placebo. We investigated whether the treatment effect of BI655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well-known role in LN pathogenesis.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"140 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793429","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}
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