Université de Paris, Unité Mixte de Recherche en Santé (UMR_S) 1134, Biologie Intégrée du Globule Rouge (BIGR), INSERM, Paris, France.
Institut National de la Transfusion Sanguine, Paris, France.
Blood. 2021 Jul 1;137(26):3660-3669. doi: 10.1182/blood.2020009810.
Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 proteins to the cell surface. Pathogenic variants in several genes that participate in GPI biosynthesis cause inherited GPI deficiency disorders. Here, we reported that homozygous null alleles of PIGG, a gene involved in GPI modification, are responsible for the rare Emm-negative blood phenotype. Using a panel of K562 cells defective in both the GPI-transamidase and GPI remodeling pathways, we show that the Emm antigen, whose molecular basis has remained unknown for decades, is carried only by free GPI and that its epitope is composed of the second and third ethanolamine of the GPI backbone. Importantly, we show that the decrease in Emm expression in several inherited GPI deficiency patients is indicative of GPI defects. Overall, our findings establish Emm as a novel blood group system, and they have important implications for understanding the biological function of human free GPI.
糖基磷脂酰肌醇（GPI）是一种糖脂，将超过 150 种蛋白质锚定在细胞表面。参与 GPI 生物合成的几个基因中的致病性变异体导致遗传性 GPI 缺乏症。在这里，我们报告说，参与 GPI 修饰的基因 PIGG 的纯合缺失等位基因负责罕见的 Emm 阴性血液表型。使用一组在 GPI-转酰胺酶和 GPI 重塑途径中均有缺陷的 K562 细胞，我们表明，Emm 抗原的分子基础几十年来一直未知，仅由游离 GPI 携带，其表位由 GPI 主链的第二和第三个乙醇胺组成。重要的是，我们表明，几个遗传性 GPI 缺乏症患者中 Emm 表达的降低表明 GPI 缺陷。总的来说，我们的发现确立了 Emm 作为一个新的血型系统，并且对理解人类游离 GPI 的生物学功能具有重要意义。
