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Lewis System

Lewis System. RBC. Lewis Antigens. Soluble antigens produced by tissues and found in body fluids (plasma) The Lewis antigens are NOT intrinsic to red cell membrane. They are produced in the plasma (Secretions) and adsorbed from the plasma onto the red cell membranes.

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Lewis System

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  1. Lewis System Mohammed Laqqan

  2. RBC Lewis Antigens • Soluble antigens produced by tissues and found in body fluids (plasma) • The Lewis antigens are NOT intrinsic to red cell membrane. • They are produced in the plasma (Secretions) and adsorbed from the plasma onto the red cell membranes. Lewis substance adheres to RBC becoming an antigen Le substance in plasma Mohammed Laqqan Le genes

  3. Lewis System: Genetics • Le gene, similar to the ABO system, codes for the production of an enzyme. • Enzyme adds Fucose to the sub terminal GlcNAc on (H) Precursor Substance to form Lea Ag. This occurs ONLY in SECRETIONS. LeaAntigen This attachment can occur ONLY on a Type 1 Chain. Why? Mohammed Laqqan

  4. Type 1 Chain: #1 carbon of Gal is attached to the #3 carbon of GlcNAc. Lewis transferase enzyme adds Fucose in an (14) linkage to make Lea antigen. It can add this fucose ONLY to the Type 1 chain. Why? Type 2 Chain: #1 carbon of Gal is attached to the #4 carbon of GlcNAc. Mohammed Laqqan

  5. Le gene enzyme adds Fucose here: Following the action of the Le gene the Se & H gene enzyme now adds a fucose to the same precursor substance in the SECRETIONS resulting in the formation of the Leb antigen. Leb Antigen What Genes are necessary for the production of Leb Ag’s? Le, H and Se genes. Remember, the Se gene codes for the presence of the H antigen in secretions! Mohammed Laqqan

  6. Lewis inheritance • Lewis system depends on Hh, Se, and Le genes • le, h, and sedo not produce products • If the Le gene is inherited, Lea substance is produced • Le, H, and Se genes must ALL be inherited to convert Lea to Leb. Examples: • Le, se, H Le (a+b-) • le, hh, se  Le (a-b-) • Le, Se, H  Le (a-b+) • le, H, Se  Le (a-b-) Mohammed Laqqan

  7. Lewis inheritance • Le and H genes in a secretor = Leb antigen • Le and H genes in a nonsecretor = Lea antigen • le is an amorph Mohammed Laqqan

  8. Lewis System: Antigens • Presence of Lea antigens is dependant on the inheritance of the Le gene. • Presence of Leb antigens is dependant on the inheritance of the Le, H and Se genes. • All are necessary to produce Leb antigens. Mohammed Laqqan

  9. Lea Lea Lea Lea Lea Lea Lea Lea Lea What Le antigens would be present in the secretions and on the RBC if you inherit the following genes? Lea Lea Lea Lea Le le, se/se & H Lea The Lewis red cell phenotype is: Le (a+ b–) Have Lea in secretions. Lea Lea Lea Lea Lea Lea Mohammed Laqqan

  10. Leb Leb Leb Leb Leb Leb Lea Leb Leb Leb What Le antigens would be present in the secretions and on the RBC if you inherit the following genes? Leb Leb Leb Lea Le le , Se se & H Leb Lea Leb Leb The Lewis red cell phenotype would be Le (a– b+). Have Lea and Leb in secretions. Leb Leb Mohammed Laqqan

  11. Lewis Phenotype Frequencies Mohammed Laqqan

  12. Lewis System: Antigens • What is missing? • Where is Le (a+b+)? • Leb antigen preferentially adsorbs onto the red cell membrane over Lea. Lea is still in the plasma but not found on the red blood cells • Lewis antigens routinely adsorb onto and elute off of the RBC membrane. • Cord blood: Le (a-b-) Mohammed Laqqan

  13. Lewis Antibodies • Anti-Lea, Anti-Leb • Most common Lewis antibody encountered • Lewis antibodies are neutralized by Lewis substances. • Usually occur naturally in those who are Le(a-b-) Mohammed Laqqan

  14. Lewis Antibodies • Other phenotypes Rarely produce the antibody • May be detected soon after pregnancy because pregnant women may temporarily become Le(a-b-) • No clinical significance…Why? • Le antibodies in a patient can be neutralized by the Lewis antigens in the donor’s plasma (cancel each other out) • do not cause HDN because they do not cross placenta (antigens not developed well in cord blood) Mohammed Laqqan

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