Differential Tissue Expression of the Lewis Blood Group Antigens: Enzymatic, Immunohistologic, and Immunochemical Evidence for Lewis a and b Antigen Expression in Le(a–b–) Individuals

The Lewis blood group system comprises two main carbohydrate antigens. Lea and Leb. Lewis typing has traditionally been based on serologic determinations using erythrocytes and saliva. Several recent studies have demonstrated that erythrocyte Lewis phenotype may change during pregnancy or disease, and inappropriate Lewis antigens have been found in both normal and neoplastic tissue. To evaluate whether these observations are in conflict with the presently proposed genetic and biosynthetic basis of the Lewis blood group system, we performed a combined enzymatic, immunohistologic, and immunochemical study of Lewis antigen expression in normal and neoplastic tissues, as well as erythrocytes, plasma, and saliva of Le(a–b–)-typed individuals. Of six cancer-bearing patients typed Le(a–b–), three were identified as nongenuine owing to the presence of α1 → 4fucosyltransferase activity (α1 → 4FT) and Lewis antigens in saliva and three were identified as genuine (lacking αl → 4FT and Lewis antigens in saliva). These genuine Le(a–b–) individuals were shown to express significant αl → 4FT in tissues, and Lewis antigens were detected in tissues by immunohistology as well as immunochemistry. We conclude that the Lewis phenotype obtained by serologic determination of erythrocytes and saliva does not apply to all tissues. We discuss biosynthetic and genetic consequences of this finding.