{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T02:45:46Z","timestamp":1780713946172,"version":"3.54.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the distributions of lymphocytes in adult onset Still\u2019s disease (AOSD) with liver dysfunction, and further prospectively explore whether receptor interacting serine\/threonine kinases (RIPKs) in lymphocytes play a role in the pathogenesis of AOSD especially liver involvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy-two AOSD patients and 19 cases of healthy controls (HCs) were retrospectively reviewed, the AOSD group was then divided into liver damage (LD) group and non-liver damage (NLD) group, and the distributions of lymphocytes in peripheral blood were analyzed. Another independent 24 AOSD patients and 20 HCs were recruited for prospective study of RIPKs; the RIPKs in peripheral blood lymphocytes were detected by flow cytometry. Liver biopsy specimens were obtained from two AOSD patients and underwent immunochemistry analysis with RIPK1 and RIPK3 antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the retrospective study, AOSD showed significantly abnormal lymphocytes distributions, and disease activity was positively correlated with percentage of CD3<jats:sup>+<\/jats:sup> T cells. LD patients were younger in age and showed higher disease activity score than NLD patients; they had higher frequencies of CD3<jats:sup>+<\/jats:sup> T cells, especially higher CD8<jats:sup>+<\/jats:sup> T cells (all <jats:italic>p<\/jats:italic>&amp;lt;0.05). In the prospective study, RIPKs in lymphocytes were significantly higher in AOSD patients than that of HCs, and LD patients also showed higher RIPKs expression than NLD patients. In addition, RIPKs were positively correlated with erythrocyte sedimentation rate (ESR) and disease activity in AOSD patients and LD and NLD subgroups (all <jats:italic>p<\/jats:italic>&amp;lt;0.05). Further, RIPKs expression was confirmed in two AOSD patients\u2019 liver. ROC curve analysis indicated that RIPKs in lymphocytes (%) could be potential biomarkers in the diagnosis of AOSD and liver damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Abnormal lymphocytes distributions and RIPKs expression were detected in AOSD. Aberrant expression of RIPKs in lymphocytes might be involved in the pathogenesis of AOSD. RIPKs could be candidate markers for AOSD and liver damage.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2020.560744","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T05:07:15Z","timestamp":1606194435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The Role of RIPK1\/3 in Adult Onset Still\u2019s Disease Patients With Liver Damage: A Preliminary 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