Final Diagnosis -- Lewis A Antibody


Contributors' Note:

The Lewis system antigens are uncommonly clinically significant; however, they are of great interest in immunohematology in that they are the only red cell antigens which are not produced by the RBC itself. The Lewis antigens originate in the body secretions, and are subsequently adsorbed onto the surface of the red cell. It has also been noted that the Le substance can dissociate from the cells just as readily; therefore, Lewis-positive donor cells can become Lewis-negative following transfusion into an individual with a Lewis-negative phenotype.1

The Lewis antigen is created within many different cells in the body (usually the same which produce ABH antigens) and secreted as a water-soluble product. The Lewis and ABH antigens share the same precursor substance, the type 1 oligosaccharide chain. The Lewis (Le) gene is located on chromosome 19 and codes for a fucosyl-transferase that attaches a fucose to the N-acetyl-glucosamine of this precursor substance.2 The secretor gene (Se) controls the secretion of ABH substances into the bodily fluids; however, Le(a+b-) individuals can still secrete Lewis a antigen into secretions despite the fact that they are all "nonsecretors" (sese). The Lea antigen is present of the red blood cell membrane only when the secretor (Se) gene is absent. However, the Lea antigen is present in the secretions whenever the Le gene is expressed. The Leb antigen is the result of genetic interaction between the Le, Se, and H genes.3 Formation of this antigen utilizes an enzyme which may also form Lea on some of the precursor substances. For this reason, although RBCs will phenotype as Le(a-b+), Lea antigen is still present in the serum in small amounts. Lewis b antigen, by virtue of its greater concentration, competes more successfully for adsorption sites on the red cell membrane. Therefore, Le(a-b+) individuals may receive blood from Le(a+b+) or Le (a+b-) donors.4

Le(a-b+)is the most common Lewis phenotype seen in the white population (75%) and the black population (55%). Le(a+b-) occurs in roughly equal proportions in both populations (23%), while Le (a-b-) is far more common in the black population (22%). Lec and Led antigens exist in individuals with the Lewis (a-b-) phenotype. In this situation, the fucosyltransferase codes for the transfer of a fucose to the third carbon of the N-acetylglucosamine of a type 2 oligosaccharide chain. Lec is present in nonsecretors (sese) and Led in secretors (Sese or SeSe). These antigens are rarely, if ever, clincally significant.5

Both anti-Lea and anti-Leb are usually "natural" in origin and of the IgM class. IgG anti-Lea has been reported, but does not bind the red blood cells as readily as the IgM, and is therefore usually only detectable using very sensitive assays. These antibodies generally are reactive in a thermal range from 4o C to 37o C. Anti-Lea and rarely anti-Leb may cause hemolysis in vivo, and the magnitude of red cell destruction is rarely of clinical importance.1 Most Lewis antibodies are of the IgM type, and are thus unable to cross the placenta; the Le antigens are also poorly formed on fetal and neonatal erythrocytes. For these reasons, Lewis antibodies have not been implicated in hemolytic disease of the newborn.

Lewis antibodies are rarely of clinical significance due to the presence of abundant Lewis substance in the serum, which may neutralize the antibodies in vitro during the crossmatch or in vivo during transfusion. For an accurate crossmatch in the laboratory, washing the red cells may be of some help. In transfusions of Le antigen positive blood to Lewis-negative recipients, the Lewis substance in plasma may reduce the effect of anti-Le antibodies on red blood cells, and thus, the recipient may avoid a more serious transfusion reaction. As a result, it is generally unnecessary to prescreen donor cells for the absence of Lewis antigens provided that a standard crossmatch is performed.6


  1. Harmening DM, Taghizadeh M: The Lewis System. In Harmening DM, (ed): Modern Blood Banking and Transfusion Practices. FA Davis, Philadelphia 1994, pp. 133-145.
  2. Oriol R: Genetic control of the fucosylation of ABH precursor chains. Evidence for new epstatic interactions in different cells and tissues. J Immunogenet 1990; 17:235.
  3. Pittiglio DH: Genetics and Biochemistry of A,B,H, and Lewis antigens. In Wallace ME and Gibbs FL (eds.): Blood Group systems: ABH and Lewis. Arlington, VA, American Association of Blood Banks
  4. Cheng MS, Lukomskyj L. Lewis antibody following a massive blood transfusion. Vox Sang 1989; 57:155.
  5. Dracker RA, Lauenstein KJ, Davey FR: Immunohematology. In Nelson DA, Tomar RH, Washington JA (eds.): Clinical Diagnosis and Management by Laboratory Methods. WB Saunders Co., Philadelphia, 1991, pp. 992-993.
  6. Widman FK: Technical Manual, 9th edition. Arlington, VA, American Association of Blood Banks, 1985.

Contributed by Kevin Horn, MD and Darrell Triulzi, MD


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