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Although antibody\u2010mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high\u2010throughput data, except for the belated emergence of autoreactive antibodies. In this study, using flow cytometry (FCM), proteomics, and single\u2010cell RNA sequencing of samples from patients with ITP, it is shown that exosome\u2010mediated lectin complement pathway is involved in the pathogenesis of ITP, which triggers and enlarges the complement activation cascade without effective regulation because of downregulated CD55. The activated complement system enhances the immune response and resistin and further Macrophage Migration Inhibitory Factor (MIF) triggers several proinflammatory signaling pathways, which contribute to the survival of hyperactivated immune cells and dysfunctional arachidonic acid (AA) metabolism. The resistin and MIF are also identified as potential contributors to resistance to glucocorticoid therapy. Taken together, the findings indicate that the lectin pathway of the complement system, resistin, MIF, and AA metabolism may serve as promising targets for ITP treatment, offering novel perspectives on potential therapeutic interventions.<\/jats:p>","DOI":"10.1002\/advs.202412378","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T13:58:24Z","timestamp":1736517504000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exosome\u2010Mediated Lectin Pathway and Resistin\u2010MIF\u2010AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia"],"prefix":"10.1002","volume":"12","author":[{"given":"Jin","family":"Li","sequence":"first","affiliation":[{"name":"Translational Medical Center The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan 450001 China"},{"name":"Department of Hematology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan 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