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The Lewis antigen system is a human blood group system. It is based upon two genes on chromosome 19: FUT3, or Lewis gene; and FUT2, or Secretor gene. Both genes are expressed in glandular epithelia. FUT2 has a dominant allele which codes for an enzyme (designated Se) and a recessive allele which does not produce a functional enzyme (designated se). Similarly, FUT3 has a functional dominant allele (Le) and a non-functional recessive allele (le).
The proteins produced by the FUT2 and FUT3 genes modify type I oligosaccharide chains to create Lewis antigens. These oligosaccharide chains are similar to the type II chains of the ABO blood system, with a single bond in a different position. The link between the Lewis blood group and secretion of the ABO blood group 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.
There are two main types of Lewis antigens, Lewis a (Le-a) and Lewis b (Le-b). There are three common phenotypes: Le(a+b-), Le(a-b+), and Le(a-b-).Mais DD. ASCP Quick Compendium of Clinical Pathology, 2nd Ed. Bethesda: ASCP Press, 2008.
The enzyme fucosyltransferase 3 (FUT3), encoded by Le gene, adds a fucose to the precursor oligosaccharide substrate, converting it to the Le-a antigen. People who have the Le allele and who are non-secretors (homozygous for the nonfunctional se allele) will express the Le-a antigen in their bodily fluids and on their erythrocytes.
If a person has both the Le and Se alleles, their exocrine cells will also have the enzyme fucosyltransferase 2 (FUT2). This adds fucose to the oligosaccharide precursor in a different position from the FUT3 enzyme. This produces the Le-b antigen. In most people having both Le and Se, it is difficult to detect the antigen Le-a. This is because the activity of the FUT2 enzyme is more efficient than the FUT3 enzyme, so the type I oligosaccharide chain is mostly converted into Le-b instead of Le-a. Therefore, people with readily detectable Lewis-a antigen are non-secretors; they do not have FUT2 activity. Lewis-b antigen is found only in secretors: people who possess the Se allele and thus have FUT2 activity. Lewis negative people (Le a-, Le b-) are homozygous for the recessive le allele and can be either secretors or non-secretors.
Le(a+b-) individuals have at least one functional Lewis gene (Le) but are homozygous for nonfunctional Secretor alleles (sese). Thus, these individuals synthesize and secrete Le(a) antigen but lack Le(b) and type 1 chain ABH.Roback JD et al. AABB Technical Manual, 16th Ed. Bethesda: AABB Press, 2008. Le(a-b+) individuals inherit both Le and Se alleles, leading to the synthesis of Le(a), Le(b), and type 1 chain ABH. Most type 1 chain precursor is converted to Le(b), therefore these individuals appear as if they are Le(a-). Le(a+b+) phenotype is transiently observed in infants (Secretor activity increases with age). This phenotype is also encountered in 16% of Japanese individuals (who inherit a weak Secretor gene- Se(w)).
In absence of a functional Lewis gene (lele), neither Le(a) nor Le(b) are synthesized, leading to the Le(a-b-) phenotype. This phenotype is more common in persons of African descent.
In neonates, i antigen oligosaccharides predominate (high in cord blood samples). Oligosaccharide branching increases with age, thus adults have mostly I antigen.
In addition, the Se gene product is responsible for the presence of A, B and H substances in secretions.
Therefore, it is not necessary to transfuse antigen-negative blood components for most patients.
Lewis antibodies are generally reactive at room temperature and only occasionally at 37 C and AHG phase (antihuman globulin).
Lewis antibodies are not a cause of hemolytic disease of the fetus and newborn (HDFN), as stated below.
Lewis antigen is often decreased on RBCs during pregnancy with some women transiently typing as Le(a-b-). This is thought to be due in part to increased circulating plasma volume in pregnancy and increased lipoprotein.
Le(b) and type 1 H antigens are also receptors for Norwalk virus (common cause of acute gastroenteritis).
The Le(a-b-) phenotype is associated with an increased susceptibility to infections by Candida and UPEC.
In patients with pancreatic adenocarcinoma and not harbouring a functional Lewis enzyme (Lea-b- genotype: 7%–10% of the population), levels of CA 19-9 are typically undetectable or below 1.0 U/ml.
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