Narimatsu H
Division of Cell Biology, Soka University, Hachioji, Japan.
Nihon Geka Gakkai Zasshi. 1996 Feb;97(2):115-22.
The biosynthetic pathways of the Lewis histo-blood type antigens, Lewis a (Le(a)) and Lewis b (Le(b)), in correlation with ABH antigen synthesis and the synthesis of sialyl Lewis antigens, sialyl Lewis a (sLe(a)) and sialy Lewis x (sLe(x)), known as tumor associated antigens are described based on the recent molecular biological studies. Individuals are divided by their erythrocyte Lewis antigen phenotypes into three types, Le (a+b-) which has Le(a) antigen but not Le(b) antigen, Le (a-b+) which has Leb but not Le(a), and Le (a-b-) having neither Le(a) nor Leb. It was verified that Le (a-b-) individuals are the homozygotes with the nonfunctional Lewis gene (Le gene) which is inactivated by the missense mutations. Two kinds of the inactivated Le gene alleles were found in the Japanese population, and named le1 and le2. Individuals having a Le (a+b-) or a Le (a-b-) -non-secretor phenotype are the mutants who lack the secretor enzyme (Se enzyme) activity. The Se gene encoding the Se enzyme has been recently cloned and analyzed for the mutation resulting in inactivation of the Se enzyme of the non-secretor individuals. Our Se gene mutant analyses on the Japanese population ensured that the Se gene is responsible for synthesis of the Le(b) antigen. Mutant analyses of the other genes, H gene and FucTVI gene, which are also involved in the synthesis of Lewis antigens are described. We recently demonstrated that the sLe(a) antigen is the product of the Lewis gene since all le/le patients, who are determined as the genuine Lewis negative individuals by Le genotyping, did not express any kinds of type 1 chain Lewis antigens (Le(a), Le(b), and sLe(a)) in their digestive organs. It is, therefore, unuseful to measure the CA19-9 titer of the genuine Lewis negative cancer patients.
基于最近的分子生物学研究，描述了Lewis血型组织抗原Lewis a（Le(a)）和Lewis b（Le(b)）的生物合成途径，以及它们与ABH抗原合成和唾液酸化Lewis抗原（唾液酸化Lewis a（sLe(a)）和唾液酸化Lewis x（sLe(x)），即肿瘤相关抗原）合成的相关性。个体根据其红细胞Lewis抗原表型分为三种类型：Le (a+b-)，具有Le(a)抗原但无Le(b)抗原；Le (a-b+)，具有Le(b)抗原但无Le(a)抗原；Le (a-b-)，既无Le(a)抗原也无Le(b)抗原。已证实Le (a-b-)个体是Lewis基因（Le基因）无功能的纯合子，该基因因错义突变而失活。在日本人群中发现了两种失活的Le基因等位基因，分别命名为le1和le2。具有Le (a+b-)或Le (a-b-)非分泌型表型的个体是缺乏分泌酶（Se酶）活性的突变体。编码Se酶的Se基因最近已被克隆，并分析了导致非分泌型个体Se酶失活的突变。我们对日本人群的Se基因突变分析证实，Se基因负责Le(b)抗原的合成。还描述了其他也参与Lewis抗原合成的基因，即H基因和FucTVI基因的突变分析。我们最近证明，sLe(a)抗原是Lewis基因的产物，因为所有通过Le基因分型确定为真正Lewis阴性个体的le/le患者，其消化器官中均未表达任何类型1链Lewis抗原（Le(a)）、Le(b)和sLe(a)）。因此，测量真正Lewis阴性癌症患者的CA19-9滴度是没有用的。
