Hashemi S, Drouin J, Trudel E, Aye M T, Couture R, Page D, Ganz P R
Ottawa Centre Blood Transfusion Service, Canadian Red Cross, Ontario.
Am J Hematol. 1991 Dec;38(4):293-303. doi: 10.1002/ajh.2830380408.
This report describes a French Canadian family whose members exhibit a high incidence of allo- and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, P1A1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia.
本报告描述了一个法裔加拿大家庭，其成员对血小板和内皮细胞上存在的抗原产生同种异体和自身抗体的发生率很高。这与已知与自身免疫相关的各种HLA特异性相关，如A1、B8、DR3，在某些情况下，还与包括肾炎、高血压和血小板减少症在内的临床疾病相关。使用血小板和内皮细胞裂解物进行的免疫印迹分析显示，血清抗体针对一种75 kDa的内皮细胞表面多肽以及在血小板和内皮细胞上均发现的表观质量为115 kDa和26 kDa的多肽。这种115 kDa的血小板内部蛋白也存在于多种其他细胞类型中，如单核细胞，并在细胞激活后增加。单克隆抗体免疫固定试验用于鉴定26 kDa的多肽；在测试的四名患者中的三名中，鉴定出一种针对白细胞分化抗原CD9的抗体。先证者的无症状儿童也表现出针对一种80 kDa血小板蛋白的自身抗体，该蛋白对凝血酶消化敏感，表明该多肽可能是血小板糖蛋白V。此外，在一名姐妹中鉴定出P1A1同种异体抗体，她曾生下一个严重血小板减少的男孩，并且在本研究前2年她自身对一具尸体肾有严重的血管排斥反应。先证者在怀孕后还患上了高血压肾病并开始依赖透析。因此，这个家庭的成员产生了多种抗体，尤其是针对血小板和内皮细胞抗原的抗体。一些受试者尽管有自身抗体但仍无症状。然而，其他一些人病情严重，他们对这些抗原的免疫反应被认为在其新生儿同种免疫性血小板减少性紫癜、高血压肾病、肾移植排斥和血小板减少症的发病机制中起了作用。
