作者:  Yangsook Koh, Atsuko Taniue, Hiroyuki Ishii等

来源:  Transfusion ,2010 June, No 6,Vol 50

背景：新生儿同种免疫血小板减少症（NAIT）是以母体抗遗传自父亲的胎儿血小板抗原的同种免疫，引起的新生儿疾病为特征的。一位健康的30岁日本母亲(Hit)在平安无事的怀孕后产下第二胎。在产后9小时，这个新生儿出现严重的瘀点，血小板计数为6×10⁹/L。

研究设计和方法：为阐明这个新生儿NAIT的病因，进行了包括血小板基因分型和序列分析在内的血清学和基因研究。此外，进行了对新抗原的血清学筛查工作。

结果：NAIT新生儿的母亲的血清含抗新生儿的人类血小板抗原的抗体。使用5分类流式细胞仪，我们把抗原定位到血小板糖蛋白。随后的血小板抗原检测单克隆抗体免疫固定和血小板免疫荧光抑制实验定位抗原到GPⅡb/Ⅲa复合物的GPⅢa的亚单位上。GPⅢa的定位用序列分析为基础的分型研究所证实，发现是在GPⅢa基因的第9外显子发生1297C＞T（407脯氨酸＞丝氨酸替代）突变。这个突变被证实是HPA-7的第三个等位基因。抗-Hita与突变的GPⅢa转染的细胞反应，但与表达野生型GPⅢa的稳定的转染子不反应。在日本人群中对Hit作血清学筛查，显示表现型频率大约为0.0015。

结论：我们发现了HPA-7的新的第三个等位基因，其特征是为在GPⅢa基因上1297C＞T的突变。这个1297C＞T等位基因在日本人群中的比例为0.15%。这抗原的抗体能引起严重的NAIT。

Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen-7

Transfusion ,2010 June NO 6,Vol 50

Yangsook Koh, Atsuko Taniue, Hiroyuki Ishii, Nobuki Matsuyama, Etsuko Amakishi, Tbmoya Hayashi, Rika A. Furuta, Yasuo Fukumori, Fumiya Hirayama, Keiji Yoshimura, Tomoko Nagamine, Susumu Tamai, and Susumu Nakano

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet (PLT) antigens inherited from the father. A healthy 30-year-old Japanese woman (Hit) gave birth to her second child after an uneventful pregnancy. Nine hours after birth, the infant presented with severe petechiae and a PLT count of 6×10⁹/L.

STUDY DESIGN AND METHODS: To elucidate the maternal cause  NAIT in the infant, serologic and genetic studies, including PLT genotyping and sequence-based analysis, were conducted. Additionally, serologic screening for the new PLT antigen was performed.

RESULTS: Serum from the NAIT infants mother contained antibodies directed against a human PLT antigen (HPA) of the newborn. Using five-cell-lineage flow cytometry we localized the antigen to a PLT glycoprotein (GP). Subsequent monoclonal antibody immobilization of PLT antigen assay and PLT immunofluorescence inhibition experiments localized the antigen to the GPⅢa subunit of the GPⅡb/Ⅲa complex. GPⅢa localization was confirmed by sequence-based typing studies, which identified a 1297C>T (407proline>serine substitution) mutation on the ninth exon of the GPⅢa gene. This mutation identified the third allele of HPA-7. Anti-Hita reacted with mutated GPⅢa -transfected cells but not with stable transfectants expressing wild-type GPⅢa. Serologic screening for Hit in the Japanese population revealed a phenotypic frequency of approximately 0.0015.

CONCLUSIONS: We identified a new third allele of HPA-7, which is characterized by a 1297C>T mutation in the GPⅢa gene. This 1297C>T allele was found in 0.15% of the Japanese population. An antibody against this antigen could be the cause of severe NAIT.