5.Rh Blood Group System

HEM 2133

Immunohaematology IImmunohaematology 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 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 negativefactor 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 ABO-

compatible blood from her husbandcompatible 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 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 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 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 locationabsence 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 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 terminologyThe 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

lociloci

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)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 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 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 In this system, each antigen is assigned a

number

Comparison of Nomenclatures of the

Rh system using Common Antigens

Fisher-Race Wiener Rosenfield

D Rh0 Rh1

C rh Rh2C rh Rh2

E rh Rh3

c hr Rh4

e hr Rh5