作者：Bertrand G, Jallu V, Saillant D等

来源：Transfusion. 2009.49(10): 2076-2083

摘要：胎/婴同种免疫血小板减少症(FNAIT)是由母亲对胎儿的血小板抗原产生同种免疫引起的，胎儿的这种血小板抗原遗传于父亲而在母亲体内不存在。

研究设计和方法：一名29岁的母亲产下一名患有严重血小板减少症的婴儿（16×10⁹ PLTs/L），进行血小板输注和免疫球蛋白注射治疗，治疗效果良好。利用母亲血清与父亲血小板进行抗原捕获试验（血小板抗原单克隆抗体[MoAb]-特异性免疫固定检测技术）表现特异阳性反应，这个特异性阳性反应只在使用配偶的血小板和一组抗GPIa/IIa 单克隆抗体(α2β1 整合素) 时出现，表明含有新的血小板抗原。

结果：核酸序列分析父亲和新生儿GPIa的cDNA序列，发现在2235位点出现一个碱基置换(2235G > T)，这种置换导致GPIa成熟蛋白Q716H氨基酸发生变化，定位于参与胶原蛋白的细胞粘附的I区外面。利用中华仓鼠卵巢细胞系(CHO) 对野生型和突变体(Q716H)进行重组体外培养分析，结果表明这个氨基酸的置换能够充分有效的诱导Cab(a)表达。CHO细胞胶原蛋白的粘附没有因为Cab的多态性和母亲的抗- Cab(a)抗体而改变，表明这种突变并不影响整合素α2β1的功能。对高加索人群进行研究，在104个没有亲缘关系的献血者中没有发现Cab(a)(+)。

结论：我们介绍了一个新的血小板抗原Cab(a)，该抗原涉及到一例严重的新生儿同种免疫血小板减少症。实验表明利用“常规”的血小板同种抗原来分析可疑病例是否患新生儿同种免疫血小板减少症是不充分的。

The new platelet alloantigen Cab a: a single point mutation Gln 716 His on the alpha 2 integrin

Bertrand G, Jallu V, Saillant D, Kervran D, Martageix C, Kaplan C. 
Transfusion. 2009.49(10):2076-2083.

Abstract: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloimmunization against fetal platelet (PLT) antigens, inherited from the father and absent from maternal PLTs.

STUDY DESIGN AND METHODS: A 29-year-old mother gave birth to a severely thrombocytopenic newborn (16 x 10(9) PLTs/L) leading to PLT transfusion therapy associated with intravenous immunoglobulins. The outcome was uneventful. Maternal serum showed a specific positive reaction with the antigen-capture assay (monoclonal antibody [MoAb]-specific immobilization of PLT antigens) only when it was tested with the paternal PLTs and a panel of MoAbs against glycoprotein (GP)Ia-IIa (alpha(2)beta(1) integrin) suggesting the implication of a new PLT antigen.

RESULTS: Nucleotide sequence analysis of GPIa cDNA of the father and newborn showed a nucleotide substitution at position 2235 (2235G > T according to the international nomenclature). This substitution induces a Q716H amino acid change in the GPIa mature protein, located outside the I domain involved in cell adhesion for collagen. In vitro analysis of recombinant Chinese hamster ovary (CHO) cells expressing wild-type or mutant (Q716H) human GPIa allowed us to demonstrate that this single amino acid substitution is responsible and sufficient for inducing Cab(a) antigen expression. Adhesion of CHO cells to collagen was not modified by the Cab polymorphism, nor by the maternal anti-Cab(a) alloantibodies, indicating that the mutation does not affect the function of integrin alpha(2)beta(1). In a Caucasian population study, none of the 104 unrelated blood donors was found to be Cab(a)(+).

CONCLUSION: We describe here a new PLT alloantigen Cab(a) involved in a severe case of FNAIT. Laboratory investigation for the "common" PLT alloantigens is no longer sufficient to evaluate neonatal alloimmune thrombocytopenia in suspected cases.

本栏目负责人：杨亚丽