{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:41:02Z","timestamp":1784288462399,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["CMUH\u2010DMR\u2010104\u2010112"],"award-info":[{"award-number":["CMUH\u2010DMR\u2010104\u2010112"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR\u2010CELL\u20101901"],"award-info":[{"award-number":["DMR\u2010CELL\u20101901"]}],"id":[{"id":"10.13039\/501100004391","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":[[2023,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The etiology underlying cases of palindromic rheumatism (PR) not associated with other rheumatic diseases in patients who are seronegative for rheumatoid factor and anti\u2013cyclic citrullinated peptide (seronegative PR) is unclear. We aimed to investigate the immune cells and genes involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single\u2010center comparative study of 48 patients with seronegative PR and 48 healthy controls. Mass cytometry and RNA sequencing were used to identify distinct immune cell subsets in blood. Among the 48 seronegative PR patients, plasma samples from 40 patients were evaluated by enzyme\u2010linked immunosorbent assay for cytokine levels, and peripheral blood samples from 25 patients were evaluated by flow cytometry for mononuclear cell subsets. Plasma samples from 21 patients were evaluated by real\u2010time polymerase chain reaction for differential gene and protein expression, and samples from 3 patients were analyzed with whole\u2010exome sequencing for gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunophenotyping revealed a markedly increased frequency of CD14+CD11b+CD36+ and CD4+CD25\u2013CD69+ cells in seronegative PR patients with active flares compared with healthy controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001 for both cell subset comparisons). Gene enrichment analyses of RNA\u2010sequencing data from sorted CD14+CD11b+CD36+ and CD4+CD25\u2013CD69+ cells showed involvement of the inflammatory\/stress response, phagocytosis, and regulation of apoptosis functional pathways. Up\u2010regulated expression of <jats:italic>CXCL16<\/jats:italic> and <jats:italic>IL10RA<\/jats:italic> was observed in monocytes from PR patients. Up\u2010regulation of <jats:italic>PFKFB3<\/jats:italic>, <jats:italic>DDIT4<\/jats:italic>, and <jats:italic>TGFB1,<\/jats:italic> and down\u2010regulation of <jats:italic>PDIA6<\/jats:italic> were found in monocytes and lymphocytes from PR patients with active flares and PR patients in intercritical periods. Plasma levels of S100A8\/A9 and interleukin\u20101\u03b2 were elevated in PR patients. Whole\u2010exome sequencing revealed novel polygenic mutations in <jats:italic>HACL1<\/jats:italic>, <jats:italic>KDM5A<\/jats:italic>, <jats:italic>RASAL1, HAVCR2<\/jats:italic>, <jats:italic>PRDM9<\/jats:italic>, <jats:italic>MBOAT4<\/jats:italic>, and <jats:italic>JRKL<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In seronegative PR patients, we identified a distinct CD14+CD11b+CD36+ cell subset that can induce an inflammatory response under stress and exert antiinflammatory effects after phagocytosis of apoptotic cells, and a CD4+CD25\u2013CD69+ T cell subset with pro\u2010 and antiinflammatory properties. Individuals with genetic mutations involving epigenetic modification, potentiation and resolution of stress\u2010induced inflammation\/apoptosis, and a dysregulated endoplasmic reticulum stress response could be predisposed to seronegative PR.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42297","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T11:44:52Z","timestamp":1657626292000},"page":"187-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Assessing the Immune Cell Subset and Genetic Mutations in Patients With Palindromic Rheumatism Seronegative for Rheumatoid Factor and Anti\u2013Cyclic Citrullinated Peptide"],"prefix":"10.1002","volume":"75","author":[{"given":"Chin\u2010An","family":"Yang","sequence":"first","affiliation":[{"name":"College of Medicine, China Medical University, Division of Laboratory Medicine, China Medical University Hsinchu Hospital, and Departments of Medical Education and Pediatrics, China Medical University Hsinchu Hospital, Zhubei City, Taiwan, and Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University  Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u2010Pi","family":"Li","sequence":"additional","affiliation":[{"name":"Rheumatic Diseases Research Center, China Medical University Hospital, Department of Pathology, School of Medicine Chung Shan Medical University and Chung Shan Medical University Hospital  Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Hua","family":"Lai","sequence":"additional","affiliation":[{"name":"College of Medicine, China Medical University, Rheumatic Diseases Research Center, China Medical University Hospital, and Rheumatology and Immunology Center, China Medical University Hospital  Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Laboratory Medicine China Medical University Hsinchu Hospital  Zhubei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien\u2010Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Laboratory Medicine China Medical University Hsinchu Hospital  Zhubei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1608-7131","authenticated-orcid":false,"given":"Joung\u2010Liang","family":"Lan","sequence":"additional","affiliation":[{"name":"College of Medicine, China Medical University, Rheumatic Diseases Research Center, China Medical University Hospital, and Rheumatology and Immunology Center, China Medical University Hospital  Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2017.09.014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0308-5"},{"key":"e_1_2_7_4_1","first-page":"808","article-title":"Palindromic rheumatism. 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