作者：Peterson JA, Gitter ML, Kanack A等

来源：Transfusion. 2010. 50(2):324-333.

背景：近来报告表明，母亲对低频血小板特异性糖蛋白多态性产生免疫导致新生儿同种免疫血小板减少症(NATP)是较以前的看法更为普遍的一个原因。

研究设计和方法：对三例生出具有明显NATP症状婴儿，但并非因母亲抗已知血小板特异同种抗原而产生同种免疫的家庭，利用血清学和分子生物学方法进行血小板和DNA分析。

结果：每个母亲抗体均只与父亲的血小板进行反应。 固相分析方法中，除了病例1(Sta)，病例2(Kno)和病例3(Nos)母亲的抗体能够识别父亲的GPIIb/IIIa。从三个父亲和两个患病的婴儿的DNA中鉴定出编码GPIIb (病例 2) 或者 GPIIIa (病例1 and 3)一个氨基酸置换的突变。三个病例的抗体均识别突变导致在相应婴儿中鉴定出多态型的重组子GPIIIa (病例 1 [Sta]和病例3 [Nos])和 GPIIb (病例 2, Kno)。100个随机选择的正常对象均没有这种父系的突变。利用酶联免疫技术和流式细胞术分析表明，在固相分析中病例1的母亲血清与父亲的GPIIIa不反应原因是单抗AP2的使用，导致母亲血清抗体与AP2竞争Sta位点。

结论：三例多态性产生的免疫引起的。利用常规的血清学和分子生物学不能解释明显的。

New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia

Peterson JA, Gitter ML, Kanack A, Curtis B, McFarland J, Bougie D, Aster R. 
Transfusion. 2010. 50(2):324-333. 
Backround: Recent reports suggest that maternal immunization against low-frequency, platelet (PLT)-specific glycoprotein (GP) polymorphisms is a more common cause of neonatal alloimmune thrombocytopenia (NATP) than previously thought. 
Study design and methods: Serologic and molecular studies were performed on PLTs and DNA from three families in which an infant was born with apparent NATP not attributable to maternal immunization against known PLT-specific alloantigens. 
Results: Antibodies reactive only with paternal PLTs were identified in each mother. In Cases 2 (Kno) and 3 (Nos), but not Case 1 (Sta), antibody recognized paternal GPIIb/IIIa in solid-phase assays. Unique mutations encoding amino acid substitutions in GPIIb (Case 2) or GPIIIa (Cases 1 and 3) were identified in paternal DNA and in DNA from two of the affected infants. Antibody from all three cases recognized recombinant GPIIIa (Case 1 [Sta] and Case 3 [Nos]) and GPIIb (Case 2, Kno) mutated to contain the polymorphisms identified in the respective fathers. None of 100 unselected normal subjects possessed the paternal mutations. Enzyme-linked immunosorbent assay and flow cytometric studies suggested that failure of maternal serum from Case 1 (Sta) to react with paternal GPIIIa in solid-phase assays resulted from use of a monoclonal antibody AP2, for antigen immobilization that competed with the maternal antibody for binding to the Sta epitope. 
Conclusion: NATP in the three cases was caused by maternal immunization against previously unreported, low-frequency GP polymorphisms. Maternal immunization against low-frequency PLT-specific alloantigens should be considered in cases of apparent NATP not resolved by conventional serologic and molecular testing.

本栏目负责人：杨亚丽