The Lewis blood group antigens, e.g. Lea and Leb, are part of carbohydrate moieties attached to lipids (fucosylated glycosphingolipids) and glycoproteins. These antigens are not intrinsic to red blood cells. Instead, they are enzymatically added to precursor molecules inside exocrine epithelial cells and, following synthesis, are excreted into various bodily fluids such as plasma from which the Lewis glycolipids are adsorbed onto the red cell membrane giving rise to the Lewis phenotypes. The glycoprotein forms mainly remain in plasma and other fluids. Lewis structures also appear on other cell surfaces and have functions in embryogenesis, tissue differentiation, tumour metastasis, inflammation, and bacterial as well as viral adhesion. The biosynthesis of the Lewis antigens is dependent on the FUT3 gene that encodes an α(1,3/4)-fucosyltransferase protein (UniProt ID P21217) which catalyses the addition of fucose to a precursor polysaccharide. The biochemistry underpinning Lewis antigen synthesis is complex and cannot be detailed fully here – for more detail, please see Kukowska-Latallo et al., 1990 (PMID: 1977660) and Henry, 1996 (PMID:15387741). The type of Lewis antigen produced in this reaction depends on the type of precursor molecule the enzyme (Fuc-TIII) interacts with. In individuals with an active FUT2 (Secretor or SE) gene, which encodes a fully active α(1,2)-fucosyltransferase (see H Blood Group System), predominantly Leb (and related Lewis antigens depending on ABO group, e.g. ALeb in group A) is made alongside trace amounts of Lea. The trace amounts of Lea produced are typically undetectable using serological methods, and usually, a Le(a–b+) phenotype is reported.