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Lewis System Mohammed Laqqan 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 RBC Le genes Le substance in plasma Mohammed Laqqan 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. Lea Antigen This attachment can occur ONLY on a Type 1 Chain. Why? Mohammed Laqqan Type 1 Chain: #1 carbon of Gal is attached to the #3 carbon of GlcNAc. Lewis transferase enzyme adds Fucose in an (14) 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 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 Mohammed Laqqan presence of the H antigen in secretions! Lewis inheritance Lewis system depends on Hh, Se, and Le genes le, h, and se do 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, hh, se Le, Se, H le, H, Se Le (a+b-) Le (a-b-) Le (a-b+) Le (a-b-) Mohammed Laqqan Lewis inheritance b Le and H genes in a secretor = Le antigen a Le and H genes in a nonsecretor = Le antigen le is an amorph Mohammed Laqqan 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 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 Lea Lea Lea Le le, se/se & H The Lewis red cell phenotype is: Le (a+ b–) Have Lea in secretions. Lea Lea Lea Lea Lea Lea Lea Lea Lea Mohammed Laqqan Leb Leb Leb What Le antigens would be present in the secretions and on the RBC if you inherit the following genes? Leb Leb Lea Leb Leb Leb Leb Leb Leb Leb Lea Le le , Se se & H The Lewis red cell phenotype would be Le (a– b+). Have Lea and Leb in secretions. Leb Lea Leb Leb Leb Leb Mohammed Laqqan Lewis Phenotype Frequencies Phenotype Whites (%) Blacks (%) Le (a+ b–) 22 23 Le (a– b+) 72 55 Le (a– b–) 6 22 Le (a+ b+) rare rare Mohammed Laqqan 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 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-) Lewis Abs Clinically Significant Seldom Abs class IgM Thermal range 4 - 22 HDNB No Transfusion Reactions Extravascular Rare Intravascular Rare Mohammed Laqqan 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