d. Secretor and Lewis Genes.
(1) Secretor (Se) genes. Products of two other independent gene loci interact
with products of the ABO and Hh alleles. The Se gene acts upon cells involved in
watery secretions, like saliva, tears, and milk, enabling them to secrete glycoproteins
with blood group activity. The A, B, and H substances of red blood cells are glycolipids,
which are soluble in organic solvents but not in water. Blood-group-active glycoproteins
have the sugar─ linkages that control antigenic identity, but the parent molecule is
water-soluble. Persons homozygous or heterozygous for Se have H substance and
either A or B substance in their saliva, depending, of course, on the presence of an H
gene and the ABO genotype. Homozygotes for sese have perfectly normal red blood
cell antigens, but lack blood group activity in their secretions. Approximately 80% of the
population is secretors, while 20 percent is nonsecretors.
(2) The Lewis gene. The third Lewis phenotype occurs when the Le gene is
absent and the amorphic le gene is present in the homozygous state giving rise to the
Lea-b- phenotype. These persons lack the Lea and Leb antigens. The Le gene product
acts upon the sugar chain that also determines A, B, and H activity, but its inheritance
and its effects are independent of ABO and Hh. The Le gene directs addition of a
fucose to the sugar (N-acetylglucosamine) adjacent to the terminal galactose. See
figure 2-2. When the fucose is present, the molecule has Lewisa activity, abbreviated
Lea. The presence or absence of H-determining fucose on the adjacent galactose has
no effect on Lea activity. Another form of Lewis activity develops if the H, Se, and Le
genes are all present. In the presence of a Se gene, an active molecule is produced
with fucose on the terminal galactose and another fucose on the adjacent N-
acetylglucosamine, creating the antigenic activity called Lewisb (Leb). Without the Se
gene, Leb activity does not develop, even if Le and H genes are present. Lewis
substances are unusual because they confer red blood cell antigenic activity without
being part of the red cell membrane. Both water-soluble and alcohol-soluble forms of
Lewis are produced. The water-soluble form exists in saliva and other secretions. The
alcohol-soluble form absorbs onto the lipid-rich red blood cell membrane, conferring
antigenic activity on these surfaces and allowing agglutination by appropriate Lewis
antibodies. With suitable manipulations, the antigens can be eluted off the cells, leaving
the cells free of Lewis activity.
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