{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T19:12:46Z","timestamp":1760987566089,"version":"3.37.3"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Predicting the efficacy of biological disease\u2013modifying antirheumatic drugs is challenging. In this study, we aimed to explore markers that predict the efficacy of abatacept in rheumatoid arthritis (RA) patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Thirty RA patients receiving abatacept were recruited, and peripheral blood mononuclear cells from the participants were subjected to DNA microarray analysis. The expression of CC chemokine receptor 4 (CCR4), which was selected by the result of DNA microarray, was determined by flow cytometry in 16 newly diagnosed treatment-na\u00efve RA patients. CCR4 expression on each helper T-cell subset was also measured.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CCR4 was upregulated in the abatacept responder. The expression levels of CCR4 were significantly correlated with the improvement of the Clinical Disease Activity Index. CCR4 expression was predominantly observed in CD4+ T cells in peripheral blood mononuclear cells. The percentage of CCR4-expressing CD4+ T cells was significantly higher in RA patients than in healthy individuals. Interestingly, Th17 and Treg cells expressed high levels of CCR4 compared to non-Th17-related helper T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CCR4 is a Th17- and Treg-related gene, and the high CCR4 expression in peripheral blood samples may predict the efficacy of abatacept in RA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mr\/road077","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T12:25:19Z","timestamp":1690460719000},"page":"700-704","source":"Crossref","is-referenced-by-count":3,"title":["CCR4 predicts the efficacy of\u00a0abatacept in\u00a0rheumatoid arthritis patients through the estimation of\u00a0Th17 and\u00a0Treg cell abundance"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8466-110X","authenticated-orcid":false,"given":"Shigeru","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keishi","family":"Etori","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koto","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Meguro","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taro","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arifumi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Suto","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"},{"name":"Graduate School of Medicine, Institute for Advanced Academic Research , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University , Chiba, Japan"},{"name":"Chiba University, Synergy Institute for Futuristic Mucosal Vaccine Research and Development (cSIMVa) , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"2024070612131761100_R1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/ard-2022-223356","article-title":"EULAR recommendations for\u00a0the management of\u00a0rheumatoid arthritis with synthetic and\u00a0biological disease-modifying antirheumatic drugs: 2022 update","volume":"82","author":"Smolen","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"2024070612131761100_R2","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1056\/NEJMoa035075","article-title":"Treatment of\u00a0rheumatoid arthritis by selective inhibition of\u00a0T-cell activation with fusion protein CTLA4Ig","volume":"349","author":"Kremer","year":"2003","journal-title":"N Engl J Med"},{"key":"2024070612131761100_R3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nri.2016.124","article-title":"The immunopathogenesis of\u00a0seropositive rheumatoid arthritis: from triggering to targeting","volume":"17","author":"Malmstrom","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"2024070612131761100_R4","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1136\/annrheumdis-2015-207942","article-title":"Impact of\u00a0baseline anti-cyclic citrullinated peptide-2 antibody concentration on\u00a0efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial","volume":"75","author":"Sokolove","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"2024070612131761100_R5","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s40744-022-00467-4","article-title":"Efficacy of\u00a0abatacept versus tumor necrosis factor inhibitors in\u00a0anti-citrullinated protein antibody-positive patients with rheumatoid arthritis: Results from a Korean nationwide biologics registry","volume":"9","author":"Kim","year":"2022","journal-title":"Rheumatol Ther"},{"key":"2024070612131761100_R6","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/mr\/roab029","article-title":"Efficacy and\u00a0safety of\u00a0abatacept in\u00a0biologic-naive patients with active rheumatoid arthritis by background methotrexate dose: post hoc analysis of\u00a0a randomized, placebo-controlled, phase 4 study","volume":"32","author":"Tanaka","year":"2022","journal-title":"Mod Rheumatol"},{"key":"2024070612131761100_R7","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1007\/s10067-021-05602-0","article-title":"High serum IgA and\u00a0activated Th17 and\u00a0Treg predict the efficacy of\u00a0abatacept in\u00a0patients with early, seropositive rheumatoid arthritis","volume":"40","author":"Inamo","year":"2021","journal-title":"Clin Rheumatol"},{"key":"2024070612131761100_R8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0215192","article-title":"Circulating Th17.1 cells as candidate for\u00a0the prediction of\u00a0therapeutic response to abatacept in\u00a0patients with rheumatoid arthritis: an exploratory research","volume":"14","author":"Maeda","year":"2019","journal-title":"PLoS One"},{"key":"2024070612131761100_R9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for\u00a0the classification of\u00a0rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum"},{"key":"2024070612131761100_R10","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.berh.2007.02.004","article-title":"The Simplified Disease Activity Index (SDAI) and\u00a0Clinical Disease Activity Index (CDAI) to monitor patients in\u00a0standard clinical care","volume":"21","author":"Aletaha","year":"2007","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2024070612131761100_R11","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/art.38400","article-title":"Prediction of\u00a0therapeutic responses to tocilizumab in\u00a0patients with rheumatoid arthritis: biomarkers identified by analysis of\u00a0gene expression in\u00a0peripheral blood mononuclear cells using genome-wide DNA microarray","volume":"66","author":"Sanayama","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"2024070612131761100_R12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1471-4892(03)00069-9","article-title":"Chemokines in\u00a0allergic airway disease","volume":"3","author":"Lloyd","year":"2003","journal-title":"Curr Opin Pharmacol"},{"key":"2024070612131761100_R13","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2015.00384","article-title":"T cell migration in\u00a0rheumatoid arthritis","volume":"6","author":"Mellado","year":"2015","journal-title":"Front Immunol"},{"key":"2024070612131761100_R14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jaut.2017.12.006","article-title":"Molecular mechanisms underpinning T helper 17 cell heterogeneity and\u00a0functions in\u00a0rheumatoid arthritis","volume":"87","author":"van Hamburg","year":"2018","journal-title":"J Autoimmun"},{"key":"2024070612131761100_R15","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1016\/j.cell.2021.03.056","article-title":"Dynamic landscape of\u00a0immune cell-specific gene regulation in\u00a0immune-mediated diseases","volume":"184","author":"Ota","year":"2021","journal-title":"Cell"},{"key":"2024070612131761100_R16","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1365-2249.2004.02617.x","article-title":"Increased CCR4 expression on\u00a0circulating CD4(+) T cells in\u00a0ankylosing spondylitis, rheumatoid arthritis and\u00a0systemic lupus erythematosus","volume":"138","author":"Yang","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"2024070612131761100_R17","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41591-022-01789-0","article-title":"Rituximab versus tocilizumab in\u00a0rheumatoid arthritis: synovial biopsy-based biomarker analysis of\u00a0the phase 4 R4RA randomized trial","volume":"28","author":"Rivellese","year":"2022","journal-title":"Nat Med"},{"key":"2024070612131761100_R18","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1093\/intimm\/dxh144","article-title":"BAZF is required for\u00a0activation of\u00a0naive CD4 T cells by TCR triggering","volume":"16","author":"Takamori","year":"2004","journal-title":"Int Immunol"},{"key":"2024070612131761100_R19","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2021.112482","article-title":"Down-regulation of\u00a0A3AR signaling by IL-6-induced GRK2 activation contributes to Th17 cell differentiation","volume":"399","author":"Hu","year":"2021","journal-title":"Exp Cell Res"}],"container-title":["Modern Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mr\/advance-article-pdf\/doi\/10.1093\/mr\/road077\/51039803\/road077.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/34\/4\/700\/58462967\/road077.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/34\/4\/700\/58462967\/road077.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T12:13:56Z","timestamp":1720268036000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mr\/article\/34\/4\/700\/7234008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":19,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,7,31]]},"published-print":{"date-parts":[[2024,7,6]]}},"URL":"https:\/\/doi.org\/10.1093\/mr\/road077","relation":{},"ISSN":["1439-7595","1439-7609"],"issn-type":[{"type":"print","value":"1439-7595"},{"type":"electronic","value":"1439-7609"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2023,7,31]]}}}