Rh Blood Group System

What are the 2 linked genes that control Rh antigens?

• Fischer Race

• Weiner

Fischer-Race vs Weiner Genetic Theories

• Fisher-Race: 3 linked loci (D/d, C/c, E/e) control Rh antigens.

• Wiener: Rh antigens controlled by alleles at one gene locus.

Fischer Race

• Each gene expresses an antigen with the same letter

  • C gene → C antigen

• Absence of D antigen: “d”.

• Gene order: usually DCE, sometimes CDE.

Wiener

8 alleles at one Rh gene locus: R0, R1, R2 , Rz, r, r′, r″, ry

• Each gene encodes an agglutinogen (factors) correlating with Rh antigens. Example 1: R1 → Rh1(Rh0, rh′ , hr″) → D, C, e

Wiener to Fisher-Race:

• R = D

• r = no D

• 1 and ′ = C

• 2 and ″ = E

• 0 = ce

• Z or y = CE

• Example: R2 → DcE

Significance of Rosenfield in phenotypes

• Antigens designated by number:

  • Rh1:D

  • Rh2:C

  • Rh3:E

  • Rh4:c

  • Rh5:e

• Example: D+, C+, E–, c+, e+ = Rh:1,2,–3,4,5

How does the ISBT standardize blood group nomenclature?

• Six-digit numbers for each blood group specificity.

• 004 = Rh system.

• The other numbers refer to the Rosenfield system

  • C antigen is RH2).

• Ex: C antigen ISBT number = 004002.

Genotype vs Phenotype

• Phenotype: result of RBCs reacting with antisera.

• Genotype: genetic makeup, predicted by phenotype and race.

Genotype

• True genotype: family studies or molecular testing.

• Common genotypes:

  • Caucasians: R1, r, R2, R0

  • Blacks: R0, r, R1, R2

  • r′, r″ , Rz , and ry are rare

Rh Genotypes and Phenotype

What are D antigens and their significance?

• Most immunogenic in Rh system.

• D-neg individuals get D-neg blood.

• D-neg individuals may produce anti-D if given D-pos blood.

  • undesired effect → hemolytic reactions

Genetics of Weak D Antigens

• More common in black population.

• Weaker form of D, often cDe haplotype.

• IAT usually needed.

• Patients are weak D pos, can receive D-pos blood.

IAT

used to detect antibodies in SERUM

Haplotype

A genetic combination of alleles at adjacent locations on a chromosome, often inherited together.

Position Effect of Weak D Antigens

• D antigen appears weak when C antigen is trans to D.

• Ce (r′) gene paired with Cde (R1) or cDe (R0).

• Patients are weak D pos, can receive D-pos blood.

Weak D: Partial D Antigens

• Individuals D pos. but missing parts of D antigen.

• Exposed to “whole D antigen,” may produce anti-D to missing part.

• Partial D antigen reacts strongly with monoclonal reagents.

• Suspect partial D when D-positive makes anti-D not reactive with own RBCs.

Weak D Significance

• AABB requires donor cells be tested for weak D if initially nonreactive.

• Recipient samples don't need weak D testing

  • classified as D-negative, transfused with D-negative blood.

Compound Antigens

AKA cis-product antigens.

• Two genes on same chromosome may form additional antigen products.

• Ex: c and e antigens cause “f” to be inherited.

G Antigens

Almost all genes coding for C or D code for G antigen.

• Anti-G antibody mimics anti-D and anti-C antibodies.

• If neg for D/C and receive D-pos/C-pos blood, may produce anti-G (appears as anti-D or anti-C).

• If anti-G present, give D-neg and C-neg blood.

Unusual Phenotypes

• D-deletion

• Rh-null

• Rh-mod

  

Rh-Ab significance

• Usually RBC stimulated

• Most are IgG1

• Agglutination best observed by IAT

• Potentiators useful for identification

• Antibodies to C, c, E, e react stronger to homozygous antigens (dosage)

• Do not activate complement

• E-neg and c-neg blood sometimes given when anti-E is identified (weak anti-c often seen with anti-E).

Clinical Considerations: Transfusion Rxns

• Rh antibody levels may be undetectable for years but produce a rapid response upon exposure to the antigen

• Ag-neg RBCs should be transfused if Rh antibodies are identified

Clinical Considerations: Hemolytic disease of the fetus and newborn (HDFN)

• HDFN may occur when a woman is Rh neg and the fetus/infant is Rh pos

• Ab may form during the 1st pregnancy

• Maternal antibody may destroy fetal RBCs in subsequent pregnancies

• Rh immune globulin will protect the mother from forming anti-D antibody

LW Blood Group System

• LW antigens/antibodies similar to Rh but not genetically related.

• Anti-LW antibody reacts with D-positive (strong) and D-negative (weak) cells.

• Alleles: Lwa , LWb , and LW

• Most common phenotype: LW