Chapter 05. Rh blood group system

Rh blood group system O complex, polymorphic, the second most important O more than 50 related antigens -> D, C, E, c, e (1) Historical Overview of the Discovery of the D Antigen O Rh positive and Rh negative: presence or absence of the D antigen O Rh antibody: require immune red cell stimulation (transfusion, pregnancy) - cause adverse transfusion reaction and HDFN - similar with antibodies made from stimulating guinea pigs and rabbits with rhesus monkey red cells (2) Genetics and Biochemistry O chromosome 1 O Fig. 5-1 upper: two gene locus, one allele for RHD, four alleles for RHCE O Fig. 5-2 O Rh antigen: polypeptide (416 amino acids, traverse membrane 12 times) carry no carbohydrate residues be detected only on red cell membranes function: cation transport and membrane integrity O Rh null: lack of Rh system antigens -> membrane abnormality -> shorten red cell survival (stomatocyte)

Rh blood group system

Rh blood group system

Rh blood group system (3) Rh Terminology O Table 5-1 1. Fisher-Race: CDE Terminology O Fig. 5-1 middle: three gene locus, each two alleles 2. Wiener: Rh-Hr Terminology O Fig. 5-1 lower: one gene locus, eight alleles O Table 5-2, Table 5-3 3. Rosenfield: Numeric Terminology O D+, C+, E-, c+, e+ -> Rh: 1,2,-3,4,5 4. International Society of Blood Transfusion: Standardized Numeric Terminology O Six-digit number - first three number: the system (004 for Rh system) - remaining three number: antigen specificity (correspond to the Rosenfield system)

Rh blood group system

Rh blood group system

Rh blood group system (4) Determining the Genotype from the Phenotype O phenotype determination: using anti-D, anti-C, anti-c, anti-E, anti-e O genotype determination: based on the frequency of gene haplotypes in a population (table 5-4, Table 5-5) - inherited as a haplotype (Fig. 5-3) - the probability of being Rh positive or Rh negative (Fig. 5-4) (5) Antigens of the Rh System 1. D Antigen O most immunogenic antigen in the Rh system O variation of the D antigen concentration in different phenotypes (Fig. 5-5) - D-deletion phenotype: the most D-antigen sites - C gene weakens the D expression if inherited on the opposite chromosome (R2R2 > R1R1)

Rh blood group system

Rh blood group system

Rh blood group system

Rh blood group system O Weak D - Du - D antigen is weakly expressed on the red cell - red cells that are positive for D only by the IAT are referred to as weak D -> when the D antigen is weakly expressed on the red cells - table 5-6 (1) weak D: genetic - Some RHD genes code for a weaker expression of the D antigen common in blacks, cDe (R0) haplotype - IAT is required (2) Weak D: position effect - when the C antigen is inherited in trans to the D antigen (Fig. 5-6) (3) Weak D: partial D - partial D: D antigen that is missing part of its typical antigenic structure - D variant or D mosaic - can make antibody to the part they are missing (4) Significance of Testing for weak D - requires testing for weak D on all donor red cells - Rh (D) control; a reagent that consists of all additives except the D antibody agglutination due to albumin, autoantibodies

Rh blood group system

Rh blood group system 2. Other Rh system Antigens O table 5-7 (1) compound antigens or cis-product antigens: the additional antigen product formed when two genes are inherited on the same chromosome (Fig. 5-7) - for example: c and e are inherited as a haplotype -> c, e, f (cis-ce) antigen (2) G antigens - genes that code for C or D antigens: code for a G antigen - anti-G: mimic anti-D and anti-C - D-negative person: C+,D- red cell transfusion -> anti-D production (actually anti-G)

Rh blood group system

Rh blood group system

Rh blood group system 3. Unusual Phenotypes (1) D-deletion phenotype - written as -D- or D-- - no reaction with anti-E, anti-e, anti-C, anti-c - deleted or nonfunctional at the RHCE site - stronger D antigen activity (Fig. 5-4) - anti-Rh17 (Hr0) production (Rh 17 antigen: present all red cell except -D- cells (2) Rhnull phenotype - have no Rh antigens - demonstrate membrane abnormality -> hemolytic anemia - negative for S, s, U, LW - anti-Rh29 (total Rh) (R h29 antigen: present on all red cells except Rhnull cells - normal regulator gene (X1r) -> (X0r): homozygous -> Rh genes are inherited but not expressed - amorph r (3) Rhmod phenotype - similar to the regulator Rhnull (XQr)

1. General Characteristics Rh blood group system (6) Rh Antibodies 1. General Characteristics O made by exposure to Rh antigens through transfusion or pregnancy O IgG, bind at 37 degrees, agglutination is observed by the IAT not associated with complement activation O dosage effect: except anti-D 2. Clinical Considerations (1) hemolytic transfusion reactions (2) Hemolytic disease of the fetus and newborn - D-positive baby vs D-negative mother - initial pregnancy: anti-D production in mother - subsequent pregnancy: anti-D -> placenta -> hemolysis of fetal RBC - Rh immune globulin (RhIG): immune serum globulin consisting of anti-D that is given to prevent the formation of anti-D by D-negative individuals - acid elution for HbF

Rh blood group system (7) LW Blood Group System O LW (Landsteiner and Wiener) O antigen, antibody: similar to Rh blood group system in serologic properteis O table 5-8 - LW(a+b-): most common - LW gene: amorph