Cines Douglas B, McMillan Robert
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Curr Opin Hematol. 2007 Sep;14(5):511-4. doi: 10.1097/MOH.0b013e3282ba5552.
This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction.
Autoantibodies are produced by a limited number of B-cell clones. Platelet antibodies may also impair megakaryocyte development and platelet turnover, thromobopoietin levels are normal or only modestly increased and a compensatory increase in platelet production is not effective in many patients. Patients may show impaired immune regulation manifested by increased proliferation of helper T lymphocytes. Cytotoxic T lymphocytes from patients can lyse platelets in vitro. If cytotoxic T lymphocytes are also capable of perturbing megakaryocyte function, this mechanism may contribute to impaired platelet production. Polymorphisms in the Fcgamma-RIIIa gene may correlate with response to certain forms of therapy and similar genetic approaches may help to identify subsets of patients that differ in their natural history and response to various interventions.
Better understanding of autoantibody development, inhibition of thrombopoiesis and Fcgamma receptor and other polymorphisms will assume increased importance in elucidating the pathogenesis and targeting treatment of chronic immune thrombocytopenic purpura.
本文总结了免疫性血小板减少性紫癜病理生理学的最新见解，这是一种针对细胞特异性糖蛋白（GPIIb-IIIa、GPIb-IX等）的自身抗体加速血小板破坏的疾病。
自身抗体由有限数量的B细胞克隆产生。血小板抗体也可能损害巨核细胞发育和血小板更新，血小板生成素水平正常或仅适度升高，许多患者中血小板生成的代偿性增加无效。患者可能表现出免疫调节受损，表现为辅助性T淋巴细胞增殖增加。患者的细胞毒性T淋巴细胞可在体外裂解血小板。如果细胞毒性T淋巴细胞也能够扰乱巨核细胞功能，这种机制可能导致血小板生成受损。Fcγ-RIIIa基因多态性可能与对某些治疗形式的反应相关，类似的基因方法可能有助于识别在自然病史和对各种干预措施反应方面存在差异的患者亚组。
更好地理解自身抗体的产生、血小板生成的抑制以及Fcγ受体和其他多态性在阐明慢性免疫性血小板减少性紫癜的发病机制和靶向治疗中将变得越来越重要。
