Blood Research Institute and Platelet & Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, Wisconsin 53201-2178, USA.
Transfusion. 2010 Feb;50(2):324-33. doi: 10.1111/j.1537-2995.2009.02438.x. Epub 2009 Oct 10.
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.
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.
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.
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.
最近的报告表明，针对低频血小板（PLT）特异性糖蛋白（GP）多态性的母体免疫是新生儿同种免疫性血小板减少症（NATP）的一个比以前认为更为常见的原因。
对三个家族的 PLT 和 DNA 进行了血清学和分子学研究，这些家族中的婴儿出生时表现出明显的 NATP，不能归因于针对已知 PLT 特异性同种抗原的母体免疫。
每个母亲的血液中都发现了仅与父系 PLT 反应的抗体。在案例 2（Kno）和案例 3（Nos）中，但不是案例 1（Sta）中，抗体在固相测定中识别了父系 GPIIb/IIIa。在父系 DNA 中以及两个受影响婴儿的 DNA 中鉴定到编码 GPIIb 中氨基酸取代的独特突变（案例 2）或 GPIIIa（案例 1 和 3）。来自所有三个案例的抗体都识别重组 GPIIIa（案例 1 [Sta]和案例 3 [Nos]）和 GPIIb（案例 2，Kno），其突变包含各自父亲中鉴定出的多态性。在 100 个未选择的正常个体中，没有一个个体具有父系突变。酶联免疫吸附测定和流式细胞术研究表明，案例 1（Sta）的母体血清在固相测定中未能与父系 GPIIIa 反应，原因是使用了用于抗原固定的单克隆抗体 AP2，该抗体与母体抗体竞争与 Sta 表位结合。
在这三个案例中，NATP 是由针对先前未报道的低频 PLT 特异性同种抗原的母体免疫引起的。在常规血清学和分子学检测无法解决的明显 NATP 病例中，应考虑针对低频 PLT 特异性同种抗原的母体免疫。
