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Bruton's tyrosine kinase (BTK) is widely expressed and essential for immune cells. Several BTK inhibitors have been used clinically to treat haematological malignancies, while few studies are focusing on the regulatory role of BTK in ITP. This study aims to explore the feasibility and underlying mechanisms of a novel BTK inhibitor orelabrutinib in the treatment of ITP through in\u00a0vitro and in\u00a0vivo experiments. Orelabrutinib could inhibit B\u2010cell receptor\u2010mediated B\u2010cell activation, proliferation, differentiation and pro\u2010inflammatory cytokine secretion. Transcriptome sequencing revealed that B cells of ITP patients were more hyper\u2010responsive in inflammation and secretion activity compared to healthy controls, and orelabrutinib might alter B\u2010cell status through downregulating ribosome and mitochondrial metabolism. Fc\u03b3 receptor\u2010mediated platelet phagocytosis and pro\u2010inflammatory cytokine production by macrophages were also suppressed by orelabrutinib. Furthermore, orelabrutinib treatment considerably elevated the platelet count in active ITP murine models by inhibiting plasma cell differentiation, anti\u2010platelet antibody production, pro\u2010inflammatory factor secretion and platelet phagocytosis in the livers and spleens. Taken together, orelabrutinib could serve as a potential therapeutic agent for ITP by blocking antibody\u2010mediated platelet destruction.<\/jats:p>","DOI":"10.1111\/bjh.20045","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:01:32Z","timestamp":1741762892000},"page":"1186-1199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of orelabrutinib, a <scp>BTK<\/scp> inhibitor, on antibody\u2010mediated platelet destruction in primary immune thrombocytopenia"],"prefix":"10.1111","volume":"206","author":[{"given":"Tian\u2010shu","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan City Shandong Province China"},{"name":"Department of Hematology The Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang Province 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