A new platelet alloantigen, Swia, located on glycoprotein Ia identified in a family with fetal and neonatal alloimmune thrombocytopenia
A new platelet alloantigen, Swia, located on glycoprotein Ia identified in a family with fetal and neonatal alloimmune thrombocytopenia
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DOI：
10.1111/j.1537-2995.2010.03038.x
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发表时间：
2011-08-01
期刊：
影响因子：
2.9
通讯作者：
Santoso, Sentot
中科院分区：
文献类型：
--
作者：
Kroll, Hartmut;Feldmann, Korinna;Santoso, Sentot
背景技术背景：胎儿和新生儿同种免疫性血小板减少症（FNAIT）是一种出血性疾病，由母体抗体经胎盘传递给血小板（PLT）表达相应人类PLT抗原（HPA）的胎儿引起。结果：经免疫组化证实，Swi（a）抗原定位于血小板膜糖蛋白（GP）IIb/IIIa（alpha（IIb）beta（3））和GPIa/IIa（alpha（2）beta（1）integrin）上，提示存在抗HPA-1a和抗GPIa的同种抗体（抗Swi（a））。对父本GPIa全长cDNA的分析显示，外显子28中的C3347 T单核苷酸取代导致Thr（1087）Met氨基酸取代。通过聚合酶链反应-限制性片段长度多态性使用MslI内切酶的家庭成员的测试表现出完美的相关性与表型。扩展的家庭和人口研究表明，10名父亲家庭成员中有4人是Swi（a）携带者，但500名无关献血者中没有一人是Swi（a）携带者。在等位基因特异性转染的中国仓鼠卵巢（CHO）细胞上的表达研究证实，单个氨基酸取代Thr（1087）Met负责Swi（a）表位的形成。表达Swi（a）同种异体抗原的CHO细胞与固定化胶原的粘附与野生型对照相比没有受损，并且不受抗Swi（a）同种异体抗体的抑制。结论：在这项研究中，我们定义了一种新的PLT同种异体抗原Swi（a），它参与了针对HPA-1a的额外免疫的情况。我们的观察结果表明，PLT特异性同种抗体的组合可能包含低频同种抗原。
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by transplacental passage of maternal antibodies to fetuses whose platelets (PLTs) express the corresponding human PLT antigen (HPA).STUDY DESIGNS AND METHODS: We observed a fetus with FNAIT who died from a severe intracranial hemorrhage. Analysis of maternal serum in antigen capture assay with paternal PLTs showed reactivity with PLT glycoprotein (GP) IIb/IIIa (alpha(IIb)beta(3)) and GPIa/IIa (alpha(2)beta(1) integrin), indicating the presence of anti-HPA-1a and an additional alloantibody against GPIa (termed anti-Swi(a)).RESULTS: By immunochemical studies, the localization of the Swi(a) antigen on GPIa/IIa could be confirmed. Analysis of paternal GPIa full-length cDNA showed a single-nucleotide substitution C3347T in Exon 28 resulting in a Thr(1087)Met amino acid substitution. Testing of family members by polymerase chain reaction-restriction fragment length polymorphism using MslI endonuclease showed perfect correlation with phenotyping. Extended family and population studies showed that 4 of 10 members of the paternal family but none of 500 unrelated blood donors were Swi(a) carriers. Expression studies on allele-specific transfected Chinese hamster ovary (CHO) cells confirmed that the single-amino-acid substitution Thr(1087)Met was responsible for the formation of the Swi(a) epitope. Adhesion of CHO cells expressing the Swi(a) alloantigen to immobilized collagens was not impaired compared to the wild-type control and was not inhibited by anti-Swi(a) alloantibodies.CONCLUSION: In this study we defined a new PLT alloantigen Swi(a) that was involved in a case of additional immunization against HPA-1a. Our observations demonstrate that combinations of PLT-specific alloantibodies may comprise low-frequency alloantigens.