Blood:血小板特异性抗体检测的新方法

2019-10-14 QQY MedSci原创

在人体内,血小板膜糖蛋白多态性具有免疫原性,是引起新生儿同种免疫性血小板减少症等疾病的重要临床免疫反应的原因。来源于携带罕见多态性个体的血小板通常难以获得,使得诊断性检测和输注匹配的血小板具有挑战性。I类HLA抗体经常出现在母体血清中,对血小板反应性同种抗体的检测带来额外的干扰。检测人血小板抗原(HPA) 3和9的同种异体抗体尤其具有挑战性,部分原因是由于位于多态氨基酸附近的细胞类型特异性聚糖的存

在人体内,血小板膜糖蛋白多态性具有免疫原性,是引起新生儿同种免疫性血小板减少症等疾病的重要临床免疫反应的原因。来源于携带罕见多态性个体的血小板通常难以获得,使得诊断性检测和输注匹配的血小板具有挑战性。I类HLA抗体经常出现在母体血清中,对血小板反应性同种抗体的检测带来额外的干扰。检测人血小板抗原(HPA) 3和9的同种异体抗体尤其具有挑战性,部分原因是由于位于多态氨基酸附近的细胞类型特异性聚糖的存在,它们共同形成了同种表位。

为了克服这些限制,研究人员生成了一系列I型HLA阴性的、O型血的、诱导多能干细胞(iPSCs),并对其进行基因编辑,使其内源性的HPA-3a同种抗原表位依次转变成HPA-3b、HPA-9a转化为HPA-9b。并使这些细胞分化成CD41+/CD42b+人巨核细胞(MKs),然后通过流式细胞仪检测可疑的抗HPA-3和HPA-9的异源抗血清,进而发现HPA-3a阳性的MKs可与HPA-3a患者的血清发生特异性反应,而HPA-3b MKs则不与HPA-3a患者的血清发生反应,而是与HPA-3b患者的血清发生特异性反应。

重要的是,表达HPA-9b的MKs与疑似抗HPA-9b的患者样本发生特异性反应,而且传统技术并不能检测出来。

在细胞表面表达完整的纯合糖蛋白同种异体抗原的特化iPSC来源的人巨核细胞,可大大提高对临床重要的、罕见的HPA特异性的同种异体抗体的检测能力。

原始出处:

Nanyan Zhang, et al.Bioengineered iPSC-derived megakaryocytes for the detection of platelet-specific patient alloantibodies.blood.2019002225. https://doi.org/10.1182/blood.2019002225

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