Rozman Primoz
Blood Transfusion Centre of Slovenia, Department of Immunohematology, Ljubljana.
Transpl Immunol. 2002 Aug;10(2-3):165-81. doi: 10.1016/s0966-3274(02)00063-1.
In this review, we describe the platelet surface molecules with special focus on the polymorphic glycoproteins giving rise to the human platelet alloantigen (HPA) system. We list the platelet glycoprotein complexes GPIa/IIa, GPIIb/IIIa, GPIb/V/IX and some other molecules, the corresponding genes that encode them and we describe their polymorphisms as well as their physiological function. Based on data obtained by serological and molecular methods, we explain how ancestral HPA alloepitopes have developed into the modern variants. We also describe the tissue distribution of these proteins, which seems to be wider than thought initially, and discuss the significance of the HPA encoding genes distribution in various populations. Methods for their determination are then described briefly Since HPA alloepitopes can induce antibodies with resulting clinical conditions such as: post-transfusion refractoriness to platelets (PTR); post-transfusion thrombocytopenic purpura (PTTP); and fetomaternal alloimmune thrombocytopenia (FMAIT), the mechanism of this alloimmunization and its prevention is described. Although the humoral arm is more important from the clinical viewpoint, the activation of the cytotoxic arm by HPA alloepitopes is also possible. These polymorphisms also seem to have a role in certain other clinical circumstances, therefore their impact on cardiovascular diseases and haemostatic disorders as well as their role in the transplantation of solid organs and bone marrow is addressed. We conclude that during the last decades, the research of the platelet membrane molecules contributed considerably to the diagnostics, prevention and therapy of the blood coagulation and haemostatic disorders, to the management of the neonatal thrombocytopenias, transfusion-related thrombocytopenias, refractoriness to platelet transfusions and autoimmune disorders. It also changed our view on the role of HPA alloepitopes in bone marrow and solid organ transplantation. In the future, this accumulated knowledge will be useful for the development of the cell-based therapies and immune modulation of both acquired and hereditary diseases.
在本综述中，我们描述了血小板表面分子，特别关注产生人类血小板同种抗原（HPA）系统的多态性糖蛋白。我们列出了血小板糖蛋白复合物GPIa/IIa、GPIIb/IIIa、GPIb/V/IX以及其他一些分子、编码它们的相应基因，并描述了它们的多态性及其生理功能。基于血清学和分子方法获得的数据，我们解释了原始HPA同种表位是如何发展为现代变体的。我们还描述了这些蛋白质的组织分布，其分布似乎比最初认为的更广泛，并讨论了HPA编码基因在不同人群中分布的意义。然后简要描述了它们的检测方法。由于HPA同种表位可诱导抗体，从而导致诸如：血小板输注后不应性（PTR）；输血后血小板减少性紫癜（PTTP）；以及胎儿-母体同种免疫性血小板减少症（FMAIT）等临床情况，因此描述了这种同种免疫的机制及其预防方法。尽管从临床角度来看体液免疫更为重要，但HPA同种表位也可能激活细胞毒性免疫。这些多态性似乎在某些其他临床情况下也起作用，因此探讨了它们对心血管疾病和止血障碍的影响以及它们在实体器官和骨髓移植中的作用。我们得出结论，在过去几十年中，血小板膜分子的研究对凝血和止血障碍的诊断、预防和治疗、新生儿血小板减少症、输血相关血小板减少症、血小板输注不应性和自身免疫性疾病的管理做出了重大贡献。它还改变了我们对HPA同种表位在骨髓和实体器官移植中作用的看法。未来，这些积累的知识将有助于基于细胞的疗法的发展以及对获得性和遗传性疾病的免疫调节。
