HEM 2133

Immunohaematology I
Lesson 5: The Rhesus Blood
Group System

Introduction of the Rh System

Discovered in 1940 by Landsteiner and Wiener
They injected rabbits and guinea pigs with the
red cells from Macacus rhesus monkeys
The resulting antibody reacted with the red
cells of 85% of New York blood donors

 Those who reacted were said to have the

Rhesus factor and were Rhesus positive, whilst
those that did not react lacked the Rhesus
factor and were Rhesus negative

 In 1939, Levine and Stetson had described an

antibody in a mother who had recently had a
stillborn fetus
The antibody caused a hemolytic transfusion
reaction when she was transfused with ABOcompatible blood from her husband
They suggested that the antibody had been
produced in response to an antigen carried by
the fetus, which had been inherited from the
father

 This antibody was shown to have the same

reaction pattern as Landsteiner and Wieners
anti-Rh
Rh hemolytic disease of newborn was
described for the first time
By 1945, the original Rh factor had been
renamed D and four more Rh antigens
discovered

 These were the antithetical antigens C and c,

and E and e
There are now 45 antigens in the Rh system
but D, C, c, E and e are the most commonly
identified and the most significant in blood
transfusion

Genetics of the Rh Blood Group System

Genes for Rh system
reside on Chromosome 1
two genes : RhD and RhCE
encode for the proteins RhD and RhCE
RhD protein carries the D antigen
RhCE protein carries the C and E antigens
C and E can present in various combinations
(e.g. CE, ce, Ce and cE)

 There is no antithetical component for the

RhD antigen
A d does not exist
If the D antigen is not present, there is a total
absence or deletion in this location
This corresponds to the Rh negative or D
negative phenotype
The lack of any antigenic material is the result
of absence of the RhD gene.

Biochemical Composition of Rh antigens

Rh antigens
Located on the surface of red blood cells
Found exclusively on red cells and not on tissue
cells or in body fluids in soluble form
Biochemical nature: protein
Integral to the red cell membrane
* This theory is supported by the fact that cells
without any Rh antigens, Rh null, present an
altered physical appearance and decreased red
cell survival

 Rh antigens are integral part of red blood cell

membrane

 Glycoproteins that are associated with the

biochemical structure of the Rh system have been
identified
These glycoproteins are not related to the antigenic
properties of any blood group system but rather
are associated with the red cell membrane
These glycoproteins play a role in association of the
RhD and Rh CE with the red cell membrane. The
glycoprotein associated with the red cell
membrane is Rh AG
Mutation or absence of these glycoproteins results
in lack of expression of any Rh antigens

Nomenclature
There are three different philosophies
regarding the Rh system of inheritance and
genetic control

The Fisher-Race terminology

The Wiener terminology

The Rosenfield terminology

The Fisher-Race Terminology

Fisher and Race viewed the Rh system as
being inherited as three closely linked sets of
alleles with little or no crossing over between
loci
5 major antigens: D, C, E, c and e
C and c are alleles or alternate forms of a gene
inherited at one locus
E and e are alleles at a third major locus

 D is the only known form of the gene

inherited at its locus and is defined by its
presence (D positive) or its absence (D
negative)
According to the Fisher-Race theory, Rh genes
are inherited as one gene complex (haplotype)
from each parent

 Each gene complex carries either D or the

absence of D (noted for convenience as d), C
or C and E or e
The d does not represent an allele or an
antigen and is used only to denote the
absence of D

 In contrast to ABO antigens, Rh antigens are

fully expressed on red cells before birth and
also on red cells of early fetuses

The Wiener Terminology

Inheritance of the Rh antigens as the products
of a single gene at a single locus
Each gene codes for an agglutinogen which
in turn was composed of multiple blood
factors
Agglutinogen corresponds to the haplotype
and blood factors as the Rh antigen
Five major antigens by Wiener are: Rh0, rh,
rh, hr and hr

 In this nomenclature, rh denotes the

equivalent to an uppercase letter in the
Fisher-Race terminology prime () is the
product of the Cc locus and double prime () is
the product of the Ee locus
Therefore, rh is the same as the C antigen and
so forth

The Rosenfield Terminology

A system of nomenclature based on the
serologic reactions of red blood cells with
known antibodies
In this system, each antigen is assigned a
number

Comparison of Nomenclatures of the

Rh system using Common Antigens
Fisher-Race

Wiener

Rosenfield

Rh0

Rh1

rh

Rh2

rh

Rh3

hr

Rh4

hr

Rh5