Lewis antigen system

The Lewis antigen system is a human blood group system based upon genes on chromosome 19 p13.3 (FUT3 or Lewis gene) and 19q13.3, (FUT2 or secretor gene). Both genes are expressed in glandular epithelia and have dominant alleles (Le and Se, respectively) coding for enzymes with fucosyltransferase activity and recessive alleles (le and se, respectively) that are not functional.

There are two main types of Lewis antigens, Lewis a (Le-a) and Lewis b (Le-b). They are red cell antigens which are not produced by the erythrocyte itself. Instead, Lewis antigens are components of exocrine epithelial secretions, and are subsequently adsorbed onto the surface of the erythrocyte.

The enzyme fucosyltransferase 3 encoded by Le gene adds a fucose to the precursor oligosaccharide substrate in subterminal position, converting it to the Le-a antigen. If a person has Le allele and is non-secretor (homozygous for the se allele), the Le-a antigen will be present in his bodily fluids and on his erythrocytes.

If a person besides Le has the allele Se (i.e. is a secretor), his exocrine cells will have also the enzyme fucosyltransferase 2, adding fucose to the oligosaccharide precursor in terminal position. The combined action of the two enzymes will produce antigen Le-b. In most people having both Le and Se, it is difficult to detect antigen Le-a because it is converted to Le-b very efficiently. Therefore, people with readily detectable Lewis a antigen are non-secretors, i.e. do not secrete A, B or H antigens, while Lewis b antigen is found only in secretors. Lewis negative people (Le a-, Le b-) are homozygous for the recessive le allele and can be either secretors or non-secretors.

The link between the Lewis blood group and secretion of the ABO blood group antigens was possibly the first example of multiple effects of a human gene. : the same enzyme (fucosyltransferase2) which converts the Le-a antigen to Le-b is also responsible for the presence of soluble A, B and H antigens in bodily fluids.