The chemical basis for expression of the sialyl-Le(a) antigen

The SLe(a) antigen, originally defined by monoclonal antibody 19-9, is a complex carbohydrate epitope that differs from the normal human blood group Lea antigen only by the presence of an additional sialic acid residue. SLe(a)-active oligosaccharides occur in both gangliosides and mucin-like glycoproteins in developing embryonic gut, as well as in many normal adult glandular tissues and secretions, but the antigen is virtually absent from normal adult gastrointestinal lumenal epithelial cells. Following malignant transformation of adult gastrointestinal lining epithelium and many other endodermally-derived glandular epithelia, SLe(a)-active mucins released from the ensuing tumor appear in blood plasma. The level of circulating SLe(a) antigen is currently being investigated as a means of following tumor recurrence, progression, and therapy. Recent studies on the biosynthesis of SLe(a) explain the observations that, 1) the antigen does not occur in individuals of Le(a-b-) blood group, and 2) individuals that belong to the Le(a+b-) blood group express SLe(a) more strongly than Le(a-b+) individuals. Further, the biosynthetic studies predict a new tumor antigen, NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1.... (the immediate precursor to SLe(a)) that should be expressed in Le(a-b-) individuals in nearly the same tissue distribution as found for the SLe(a) antigen in Le(a+b-) and Le(a-b+) individuals. Based upon studies of SLe(a) expression in normal saliva and the pathway for biosynthesis of SLe(a), it seems likely that future clinical studies could be profitably directed towards improving the predictive value of the plasma SLe(a) level by adjusting the quantitative results according to the Lewis blood group and ABH secretor phenotype of the individual patient.