免疫性血小板减少症(ITP)是一种常见的自身免疫性出血性疾病，抗体介导的血小板破坏是ITP血小板主要的清除方式。血小板表面糖蛋白 GPIIbIIIa 和GPIb-IX复合体是两个血小板表面的主要自身抗原。约50%-70%的患者体内可以检测到针对血小板膜糖蛋白抗原的自身抗体，血小板表面的自身抗原主要分属于两个不同的蛋白家族：大约70-80%ITP患者体内有针对GPIIbIIIa的抗体（纤维蛋白原受体），20-40%的患者被检测到针对GPIb-IX复合体（VWF受体）的抗体。近年来，我们和国内外研究者均发现不同抗体介导的血小板清除可能通过不同机制。我们的前期实验观察到，抗GPIbα抗体可以对血小板功能产生影响，而这具有结合位点特异性。本研究通过研究抗体介导ITP的发病机制不同，区分不同自身抗体在疾病的分子学机制，为ITP的分层治疗提供新的依据。

ITP is an autoimmune disorder characterized by the presence of anti-platelet autoantibodies, which bind one’s own platelets. GPIIbIIIa and GPIb-IX complex are the major autoantigens targeted on platelets. Studies have shown that over 70% of patients had platelet autoantibodies against aIIbβ3, while autoantibodies targeting the GPIb complex were detected in approximately 20- 40% patients. The current understanding of platelet destruction in ITP is that the mechanisms are mediated by an Fc-dependent pathway, in which antibodies opsonize platelets, which are subsequently engulfed and cleared by macrophages. We previously demonstrated using a murine model that anti-GPIba may cause platelet destruction through a different (i.e. Fc-independent) pathway than anti-GPIIbIIIa-mediated ITP. A significant number of monoclonal antibodies (mAbs) against GPIba can activate platelets or lead to platelet apoptosis. In this study, we hypothesized that different antibodies may have distinct mechanisms of inducing ITP that will have varying responses to therapies.