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Isolated rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of synucleinopathies, including PD. Elucidating the peripheral adaptive immune system is crucial in iRBD, but current knowledge remains limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to characterize peripheral lymphocyte profiles in iRBD patients compared with healthy control subjects (HCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross\u2010sectional study recruited polysomnography\u2010confirmed iRBD patients and age\u2010 and sex\u2010matched HCs. Venous blood was collected from each participant. Flow cytometry was used to evaluate surface markers and intracellular cytokine production in peripheral blood mononuclear cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010four iRBD patients and 36 HCs were included. Compared with HCs, patients with iRBD exhibited significant decreases in absolute counts of total lymphocytes and CD3<jats:sup>+<\/jats:sup> T cells. In terms of T cell subsets, iRBD patients showed higher frequencies and counts of proinflammatory T helper 1 cells and INF\u2010\u03b3<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells, along with lower frequencies and counts of anti\u2010inflammatory T helper 2 cells. A significant increase in the frequency of central memory T cells in CD8<jats:sup>+<\/jats:sup> T cells was also observed in iRBD. Regarding B cells, iRBD patients demonstrated reduced frequencies and counts of double\u2010negative memory B cells compared with control subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated alterations in the peripheral adaptive immune system in iRBD, specifically in CD4<jats:sup>+<\/jats:sup> and INF\u2010\u03b3<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cell subsets. An overall shift toward a proinflammatory state of adaptive immunity was already evident in iRBD. These observations might provide insights into the optimal timing for initiating immune interventions in PD. \u00a9 2024 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29798","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T06:20:07Z","timestamp":1711434007000},"page":"1179-1189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Alterations of Peripheral Lymphocyte Subsets in Isolated Rapid Eye Movement Sleep Behavior Disorder"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-6694","authenticated-orcid":false,"given":"Yuanchu","family":"Zheng","sequence":"first","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yatong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Cai","sequence":"additional","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Kou","sequence":"additional","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital 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