Rh Blood Group System
The Rh blood group system is the second most important system and is the most complex. It is important because it is associated with hemolytic transfusion reactions and with development of severe hemolytic disease of the newborn (HDN). Rh antigens are proteolipids and lack carbohydrate.
The inheritance of Rh antigens is determined by a complex of 2 closely linked genes on chromosome 1. One gene codes for the protein carrying D expression; the other codes for the proteins carrying C or c and E or e expression. Rh-positive individuals have both a D and a CE gene while Rh-negative individuals have only a CE gene. Depending on which genes are present on a chromosome, 8 common antigen combinations or haplotypes are possible: Dce, DCe, DcE, DCE, dce, dCe, dcE, dCE. Common phenotypes and genotypes are given below.
D antigen is the most important Rh antigen. Presence of a single D antigen confers upon an individual the designation Rh-positive; its absence means that the person is Rh-negative. Eighty five percent of Caucasians, 92% of African Americans and 99% of Asian Americans are Rh positive. The letter d is commonly used to indicate the lack of D in Rh-negative individuals, but neither d antigen nor anti-d has been detected.
The Fisher-Race nomenclature has been more widely adopted over the more complex Wiener nomenclature for Rh antigens. However, an abbreviated version of the Wiener system is useful to describe Rh genotypes. Wiener is covenient because it uses a single letter, R or r, with superscripts to name a 3 locus haplotype. It is possible to translate from one nomenclature to the other by remembering a few rules:
- In the Wiener system, D is indicated by an uppercase R and the absence of D is indicated by lower case r.
- In the Wiener system, superscripts or numbers are used to indicate which Cc or Ee genes are present. Numbers are used with R and primes are used with r.
- In the Fisher Race system, loci are lined up in the order Dd, Cc, Ee (e.g. DCE)
- In the Wiener system, the Dd position is numbered 0, Cc position is 1 and Ee position is 2.
- The Wiener superscript of 0, 1, 2 indicates which of the Fisher Race loci is in its uppercase form (D, C, or E). For example, 1 or prime indicates that C is capitalized, while a 2 or double prime indicates that E is capitalized.
Rh Nomenclature and Haplotype Frequencies
|
Fisher Race |
Wiener |
% Caucasians |
% African Americans |
% Asian Americans |
|
Dce |
Ro |
4 |
44 |
3 |
|
DCe |
R1 |
42 |
17 |
70 |
|
DcE |
R2 |
14 |
11 |
21 |
|
DCE |
Rz |
0.2 |
0 |
1 |
|
dce |
r |
37 |
26 |
3 |
|
dCe |
r’ |
2 |
2 |
2 |
|
dcE |
r” |
1 |
0 |
0 |
|
dCE |
ry |
0 |
0 |
0 |
The most common haplotye in Caucasians and Asian Americans is DCe (R1), while the most common phenotype in African Americans is Dce (Ro). Red blood cells that fail to react with all Rh antibodies are called Rh null. An individual’s genotype can only be determined with certainty by performing DNA analysis and family studies.
Unlike the ABO naturally occurring antibodies, Rh antibodies are produced in response to an incompatible transfusion or pregnancy. The D antigen is the most immunogenic of the Rh antigens, causing immunization at least 50% of the time when a D-negative person receives a single unit of D-positive blood. Anti-c is the second most important Rh antibody. Although anti-E is more common than anti-c, anti-E is frequently a naturally occurring antibody. Anti-c and anti-e only occur after an antigenic stimulus. Antibodies to Rh antigens are primarily IgG antibodies which can cross the placenta and hemolyze the red cells of the fetus, resulting in HDN.
