{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:29:48Z","timestamp":1787509788055,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Recent advances in single\u2010cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Synovial tissues were obtained from East Asian patients in Japan with RA (n\u00a0=\u00a041) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single\u2010cell\u2013based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin\u2013sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA\u2010DRA\n                      <jats:sup>high<\/jats:sup>\n                      synovial fibroblasts, autoimmune\u2010associated B cells,\n                      <jats:italic>GZMK<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>GZMB<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, interleukin (IL)1\u2010\u03b2\n                      <jats:sup>+<\/jats:sup>\n                      monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)\u2010\u03b1, interferons (IFNs), and IL\u20106 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the\n                      <jats:italic>IRF4<\/jats:italic>\n                      gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL\u20106 signaling, and expression of molecules associated with degeneration, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42642","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T15:38:00Z","timestamp":1688139480000},"page":"2130-2136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a\n                    <scp>Cell\u2010Type<\/scp>\n                    Deconvolution Approach"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5119-2079","authenticated-orcid":false,"given":"Sotaro","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineto","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology and Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryochi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harumi","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Kasai","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8082-1009","authenticated-orcid":false,"given":"Keita","family":"Ninagawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4705-341X","authenticated-orcid":false,"given":"Yuichiro","family":"Fujieda","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Aizaki","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Applied Immunology, Faculty of Medicine Saitama Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Applied Immunology, Faculty of Medicine Saitama Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Rheumatology Juntendo University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiryo","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Artificial Intelligence Medicine, Chiba University Graduate School of Medicine, Chiba, Japan and Advanced Data Science Project RIKEN Information R&amp;D and Strategy Headquarters, RIKEN  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Rheumatology Juntendo University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Mimura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Applied Immunology, Faculty of Medicine Saitama Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Ohmura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Morinobu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Atsumi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine University of Occupational and Environmental Health  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-8218","authenticated-orcid":false,"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-9414","authenticated-orcid":false,"given":"Sakae","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Okamura","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-5254","authenticated-orcid":false,"given":"Keishi","family":"Fujio","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214539"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4555"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01789-0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0378-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqab056"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218189"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2022.104533"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27230"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23042084"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-219065"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15383-w"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200785"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22748"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0056-8"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42642","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:33:02Z","timestamp":1759951982000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.42642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,5]]},"references-count":15,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/art.42642"],"URL":"https:\/\/doi.org\/10.1002\/art.42642","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,5]]},"assertion":[{"value":"2022-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}