Chapter 107. Transfusion Biology and Therapy (Part 2)

Rh System The Rh system is the second most important blood group system in pretransfusion testing. The Rh antigens are found on a 30- to 32-kDa RBC membrane protein that has no defined function. Although 40 different antigens in the Rh system have been described, five determinants account for the vast majority of phenotypes. The presence of the D antigen confers Rh "positivity," while persons who lack the D antigen are Rh negative. Two allelic antigen pairs, E/e and C/c, are also found on the Rh protein. The three Rh genes, E/e, D, and C/c, are arranged in tandem...
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Chapter 107. Transfusion Biology and Therapy (Part 2) Chapter 107. Transfusion Biology and Therapy (Part 2) Rh System The Rh system is the second most important blood group system inpretransfusion testing. The Rh antigens are found on a 30- to 32-kDa RBCmembrane protein that has no defined function. Although >40 different antigens inthe Rh system have been described, five determinants account for the vastmajority of phenotypes. The presence of the D antigen confers Rh positivity,while persons who lack the D antigen are Rh negative. Two allelic antigen pairs,E/e and C/c, are also found on the Rh protein. The three Rh genes, E/e, D, and C/c,are arranged in tandem on chromosome 1 and inherited as a haplotype, i.e., cDE orCde. Two haplotypes can result in the phenotypic expression of two to five Rhantigens. The D antigen is a potent alloantigen. About 15% of individuals lack thisantigen. Exposure of these Rh-negative people to even small amounts of Rh-positive cells, by either transfusion or pregnancy, can result in the production ofanti-D alloantibody. Other Blood Group Systems and Alloantibodies More than 100 blood group systems are recognized, composed of more than500 antigens. The presence or absence of certain antigens has been associated withvarious diseases and anomalies; antigens also act as receptors for infectiousagents. Alloantibodies of importance in routine clinical practice are listed in Table107-1. Table 107-1 RBC Blood Group Systems and Alloantigens Blood Antigen Alloantibody ClinicalGroup System Significance Rh (D, RBC protein IgG HTR, HDNC/c, E/e) Lewis Oligosaccharide IgM/IgG Rare HTR(Lea, Leb) Kell RBC protein IgG HTR, HDN(K/k) Duffy RBC protein IgG HTR, HDN(Fya/Fyb) Kidd RBC protein IgG HTR (often(Jka/Jkb) delayed), HDN (mild) I/i Carbohydrate IgM None MNSsU RBC protein IgM/IgG Anti-M rare HDN, anti-S, -s, and -U HDN, HTR Note: RBC, red blood cell; HDN, hemolytic disease of the newborn; HTR,hemolytic transfusion reaction. Antibodies to Lewis system carbohydrate antigens are the most commoncause of incompatibility during pretransfusion screening. The Lewis gene productis a fucosyl transferase and maps to chromosome 19. The antigen is not an integralmembrane structure but is adsorbed to the RBC membrane from the plasma.Antibodies to Lewis antigens are usually IgM and cannot cross the placenta. Lewisantigens may be adsorbed onto tumor cells and may be targets of therapy. I system antigens are also oligosaccharides related to H, A, B, and Le. I andi are not allelic pairs but are carbohydrate antigens that differ only in the extent ofbranching. The i antigen is an unbranched chain that is converted by the I geneproduct, a glycosyltransferase, into a branched chain. The branching processaffects all the ABH antigens, which become progressively more branched in thefirst 2 years of life. Some patients with cold agglutinin disease or lymphomas canproduce anti-I autoantibodies that cause RBC destruction. Occasional patients withmononucleosis or Mycoplasma pneumonia may develop cold agglutinins of eitheranti-I or anti-i specificity. Most adults lack i expression; thus, finding a donor forpatients with anti-i is not difficult. Even though most adults express I antigen,binding is generally low at body temperature. Thus, administration of warm bloodprevents isoagglutination. The P system is another group of carbohydrate antigens controlled byspecific glycosyltransferases. Its clinical significance is in rare cases of syphilisand viral infection that lead to paroxysmal cold hemoglobinuria. In these cases, anunusual autoantibody to P is produced that binds to RBCs in the cold and fixescomplement upon warming. Antibodies with these biphasic properties are calledDonath-Landsteiner antibodies. The P antigen is the cellular receptor ofparvovirus B19 and also may be a receptor for Escherichia coli binding tourothelial cells.