Cartron J P
INSERM U76, Institut National de la Transfusion Sanguine, Paris.
Transfus Clin Biol. 1996;3(3):181-210. doi: 10.1016/s1246-7820(96)80036-x.
Biochemical and molecular genetic studies have contributed to our molecular knowledge of blood group-associated molecules in the past few years. Among the 23 blood group systems presently identified, almost all have a molecular basis and present investigations are oriented towards the analysis of genetic polymorphisms, tissue-specific expression and structure-function relationships. Antigens defined by carbohydrate structures, among which ABO, Hh, Lewis and Secretor are the main representative species, are indirect gene products. They are synthesized by Golgi-resident glycosyltransferases, which are the direct products of the blood group genes. Many of these enzymes have been cloned and the molecular basis of the silent phenotypes, for instance 0, Bombay/paraBombay, Le(a-b-) and non-secretor, has been elucidated. However, the glycosyltransferases involved in the biosynthesis of Pk, P and P1 antigens are not yet characterized. A large number of blood group antigens carried by red cell polypeptides expressed at the cell surface are not related to a carbohydrate structure, and these proteins are direct blood group gene products. Most have been cloned and characterized recently, for instance MN antigens (glycophorin A), Ss antigens (glycophorin B), Gerbich antigens (glycophorins C and D) and antigens encoded by the RH, LW, KEL, FY, JK, XG, LU and XK loci. Other antigens have been located on proteins already identified, for instance the Cromer antigens on DAF, Knops antigens on CR1, Indian and AnWj antigens on CD44, Yt antigens on AChE, Diego, Wr, Rga and Warr on Band 3, Colton antigens on AQP-1 (water channel). The SC (Scianna) et DO (Dombrock) systems, however, still resist to molecular cloning. On the basis of this information, a tentative classification of blood group antigens into five functional categories is emerging: - Transporters and channels, - Receptors and ligands, - Adhesion molecules, - Enzymes, - Structural proteins. This review will focus on these recent findings and will illustrate how these studies may bring new information for analysis of normal and abnormal phenotypes and for understanding both the mechanisms of tissue specific expression and the potential function of these antigens, particularly those expressed in non-erythroid lineage. In addition, since our knowledge of the molecular basis of blood group polymorphisms has significantly increased, new genotyping techniques potentially useful in clinical applications will become available.
在过去几年中，生化和分子遗传学研究增进了我们对血型相关分子的分子层面的认识。在目前已确定的23个血型系统中，几乎所有系统都有分子基础，目前的研究方向是分析基因多态性、组织特异性表达以及结构与功能的关系。由碳水化合物结构定义的抗原，其中ABO、Hh、Lewis和分泌型是主要代表类型，它们是间接基因产物。它们由驻留在高尔基体的糖基转移酶合成，而这些糖基转移酶是血型基因的直接产物。许多此类酶已被克隆，沉默表型（如O型、孟买/类孟买型、Le(a-b-)和非分泌型）的分子基础也已阐明。然而，参与Pk、P和P1抗原生物合成的糖基转移酶尚未得到表征。大量由细胞表面表达的红细胞多肽携带的血型抗原与碳水化合物结构无关，这些蛋白质是血型基因的直接产物。其中大多数最近已被克隆和表征，例如MN抗原（血型糖蛋白A）、Ss抗原（血型糖蛋白B）、Gerbich抗原（血型糖蛋白C和D）以及由RH、LW、KEL、FY、JK、XG、LU和XK基因座编码的抗原。其他抗原已定位在已鉴定的蛋白质上，例如衰变加速因子（DAF）上的克罗马（Cromer）抗原、补体受体1（CR1）上的诺普斯（Knops）抗原、CD44上的印度（Indian）和AnWj抗原、乙酰胆碱酯酶（AChE）上的Yt抗原、带3（Band 3）上的迭戈（Diego）、Wr、Rga和Warr抗原、水通道蛋白1（AQP-1，水通道）上的科尔顿（Colton）抗原。然而，SC（斯恰纳，Scianna）和DO（多姆布罗克，Dombrock）系统仍难以进行分子克隆。基于这些信息，一种将血型抗原初步分类为五个功能类别的分类方法正在形成：- 转运蛋白和通道，- 受体和配体，- 黏附分子，- 酶，- 结构蛋白。本综述将聚焦于这些最新发现，并阐述这些研究如何为正常和异常表型的分析以及理解这些抗原（特别是在非红细胞谱系中表达的抗原）的组织特异性表达机制和潜在功能带来新信息。此外，由于我们对血型多态性分子基础的认识显著增加，临床上可能有用的新基因分型技术将应运而生。
