Arthritis & Rheumatology最新文献

{"title":"Comment on: Targeting long non‐coding RNA H19 in Subchondral Bone Osteocytes Alleviates Cartilage Degradation in Osteoarthritis","authors":"An‐Fang Huang, Wang‐Dong Xu","doi":"10.1002/art.43101","DOIUrl":"https://doi.org/10.1002/art.43101","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"112 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874268","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":"Metabolic Stress expands Polyfunctional, Proinflammatory Th17 cells in Psoriatic Arthritis, where there is IL‐23‐independent IL‐17 production","authors":"Carmel B. Stober, Louise Ellis, Jane C. Goodall, Marc Veldhoen, J.S. Hill Gaston","doi":"10.1002/art.43095","DOIUrl":"https://doi.org/10.1002/art.43095","url":null,"abstract":"ObjectiveGenetic associations and blockade of the interleukin‐23/IL‐17 axis with monoclonal antibodies support a role for this pathway in psoriatic arthritis (PsA). This study examines the requirement of IL‐23 for IL‐17 production, and the role of the metabolic microenvironment in the expansion of Th<jats:sub>17</jats:sub>‐derived cells in PsA.MethodsPsA patient synovial fluid or peripheral blood Th<jats:sub>17</jats:sub> cell frequencies were evaluated by flow cytometry using CCR6, CD161 and T‐bet as phenotypic markers, and the cytokines IFN‐γ, GM‐CSF and IL‐17 assessed by flow cytometry and ELISA. The impact of IL‐23 and metabolic stress on T cell differentiation was investigated.ResultsPolyfunctional IL‐17<jats:sup>pos</jats:sup> CD4 (p&lt;0.0001) &amp; CD8 (p&lt;0.0001), and GM‐CSF<jats:sup>pos</jats:sup> Th<jats:sub>17</jats:sub>‐derived (p&lt;0.0001) cells were increased in inflamed joints of patients with PsA, with a proportional decrease in patient peripheral blood. We demonstrate IL‐23‐independent IL‐17 release by PsA patient CD4 T cells, where the absence of IL‐23 during Th<jats:sub>17</jats:sub> differentiation reduced IL‐17 by 31±5.8%. Exogenous IL‐23 increased IL‐17, negatively regulated GM‐CSF and co‐operated with TGF‐β to augment IL‐17. Polyfunctional Th<jats:sub>17</jats:sub> and Th<jats:sub>17</jats:sub>‐derived cells, but not Th<jats:sub>1</jats:sub> cells, were expanded by metabolic stress in patients with PsA.ConclusionsWe confirmed the abundance of polyfunctional Type<jats:sub>17</jats:sub> CD4 and CD8 cells in PsA inflamed joints. We demonstrate IL‐23‐independent expansion of Th<jats:sub>17</jats:sub> cells, where IL‐23 negatively regulates GM‐CSF. This may account for therapeutic differences in IL‐17 and IL‐23 inhibition in PsA and the Spondyloarthritides. Polyfunctional IL‐17<jats:sup>pos</jats:sup> Th<jats:sub>17</jats:sub>, and Th<jats:sub>17</jats:sub>‐derived but not Th<jats:sub>1</jats:sub> cells, were expanded by metabolic stress, where metabolic stress may itself represent a unique therapeutic target.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"48 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874317","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":"Expert Perspective: Management of Relapses in Giant Cell Arteritis","authors":"Marco A Alba, Sebastian Unizony, Kenneth J. Warrington, Giuseppe Murgia, Sergio Prieto‐González, Carlo Salvarani, Eric L. Matteson, Tanaz A Kermani","doi":"10.1002/art.43098","DOIUrl":"https://doi.org/10.1002/art.43098","url":null,"abstract":"Giant cell arteritis (GCA) is a relapsing large‐vessel vasculitis with risk of serious ischemic manifestations including vision loss and vascular damage in the form of large‐artery stenosis, aneurysms and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life‐ or organ‐threatening presentations and can be controlled successfully, frequent relapses may lead to increased use of GC and consequent treatment‐related morbidity, in addition to risk of further vascular damage. Emerging data suggests that persistent disease activity may lead to increased vascular morbidity. Additionally, while tocilizumab decreases the frequency of relapses, more than 50% of patients relapse after discontinuation of therapy. Therefore, while interleukin‐6 blockade suppresses disease activity, it does not restore tolerance. In this article, we discuss the practical diagnosis and management of GCA relapses from an expert perspective. Current treatment options for GCA relapses, including those recommended by international guidelines, and novel potential therapies are reviewed.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"201 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874320","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":"Transient perivascular inflammation of the carotid artery (TIPIC) syndrome","authors":"Neeharika Namineni, Sowmya Mahalingam, Abhijeet Danve","doi":"10.1002/art.43093","DOIUrl":"https://doi.org/10.1002/art.43093","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"61 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874318","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":"Synovial innate immune exhaustion is associated with worse pain in knee osteoarthritis","authors":"Holly T. Philpott, Trevor B. Birmingham, Garth Blackler, J. Daniel Klapak, Alexander J. Knights, Easton C. Farrell, Benoit Fiset, Logan A. Walsh, J. Robert Giffin, Edward M. Vasarhelyi, Steven J. MacDonald, Brent A. Lanting, Tristan Maerz, C. Thomas Appleton","doi":"10.1002/art.43089","DOIUrl":"https://doi.org/10.1002/art.43089","url":null,"abstract":"Uncontrolled pain remains a major clinical challenge in the management of knee osteoarthritis (OA), the most common disabling joint disease. Worse pain is associated with synovial innate immune cell infiltration (synovitis), but the role of innate immune regulatory cells in pain is unknown. Our objective was to identify synovial innate immune cell subsets and pathophysiologic mechanisms associated with worse pain in patients with knee OA.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"53 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841779","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":"Endogenous retroelement activation is implicated in IFN‐α production and anti‐CCP autoantibody generation in early Rheumatoid Arthritis","authors":"Faye AH Cooles, Gemma V Pedrola, Najib Naamane, Arthur G Pratt, Ben Barron‐Millar, Amy E Anderson, Catharien MU Hilkens, John Casement, Vincent Bondet, Darragh Duffy, Fan Zhang, Ruchi Shukla, John D Isaacs","doi":"10.1002/art.43083","DOIUrl":"https://doi.org/10.1002/art.43083","url":null,"abstract":"ObjectivesEndogenous retroelements (EREs) stimulate type 1 interferon (IFN‐I) production but have not been explored as potential interferonogenic triggers in Rheumatoid Arthritis (RA). We investigated ERE expression in early RA (eRA), a period where IFN‐I is increased.MethodsERE expression (LTR5, LINE1, SINE) in disease modifying treatment naïve eRA whole blood and bulk synovial tissue was examined by RT‐PCR and Nanostring alongside IFN‐α activity. Circulating lymphocyte subsets, including B cell subsets, from eRA patients and early psoriatic arthritis (ePsA), were flow cytometrically sorted and similarly examined. Existing established RA and osteoarthritis (OA) synovial single‐cell sequencing data was re‐interrogated to identify repeat elements, and associations explored.ResultsThere was significant co‐expression of all ERE classes and <jats:italic>IFNA</jats:italic> in eRA synovial tissue (n=22, p&lt;0.0001) and significant positive associations between whole blood LINE1 expression (n=56) and circulating IFN‐α protein (p=0.018) and anti‐CCP titres (p&lt;0.0001). ERE expression was highest in circulating eRA B‐cells, particularly naïve B‐cells compared with ePsA, with possible ERE regulation by SAMDH1 implicated and associations with <jats:italic>IFNA</jats:italic> again observed. Finally, in established RA synovium, LTRs, particularly ERVK, were most increased in RA compared with OA where, for all synovial subsets (monocytes, B‐cells, T‐cells and fibroblasts), ERE expression associated with increased IFN‐I signalling (p&lt;0.001).ConclusionsPeripheral blood and synovial ERE expression is examined for the first time in eRA highlighting both a potential causal relationship between ERE and IFN‐I production and an intriguing association with anti‐CCP autoantibodies. This suggests EREs may contribute to RA pathophysiology with implications for future novel therapeutic strategies.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832080","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":"Short‐term risk of cardiovascular events in people newly diagnosed with gout: comment on the article by Cipolletta et al.","authors":"Zichang Liu, Yanwei Zhu, Hui Zhao","doi":"10.1002/art.43091","DOIUrl":"https://doi.org/10.1002/art.43091","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825168","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":"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}

{"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}

{"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}