HEM 2133

Immunohaematology IImmunohaematology I

Lesson 6: The Rhesus Blood

Group System II

The Rh (D) Antigen

Most clinically significant non-ABO red blood

cell blood group antigen

More than 50% of Rh-negative people will

form anti-D after a single exposure to Rh-form anti-D after a single exposure to Rh-

positive blood

In the routine blood bank, anti-D is the most

frequently encountered unexpected and

clinically significant antibody seen in

pretransfusion testing

The D Mosaic

The D antigen is a mosaic; that is, it is

composed of several component antigens that

are usually inherited as a block and comprise

the entire D entity

Most people inherit all of these (Rh-positive) Most people inherit all of these (Rh-positive)

or none of them (Rh-negative)

Occasionally, an individual inherits only some

of the component parts, resulting in an

incomplete D antigen

These people are referred to as D mosaic

2 theories:

Wiener and Unger: the D antigen is composed

of four component parts, RhA, RhB, RhC and

RhD

Usually, D-positive people inherit RhABCDUsually, D-positive people inherit Rh

The D mosaic or D variant people lack one or

more of the four components

These variants may form an antibody to the

component they lack

For example a person lacking RhA would be

classified as RhaBCD and could make anti- RhA if

transfused with D-positive blood with the RhA

component component

This antibody would mimic anti-D on a routine

antibody identification

Tippett and Sanger decribe six categories of D

antigen variants as categories I, II, III, IV, V and

VI

Categories are differentiated on the basis of Categories are differentiated on the basis of

reactions with many anti-D sera, the presence

of rare Rh system antigens on the blood cells

and the production of anti-D-like antibodies

Individuals who lack portions of the D antigen

structure are referred to as partial D

Individuals with DVI variant are able to

produce anti-D antibody against the missing

part of the antigen if exposed to D+ve antigen

Such recipient should be considered as Rh Such recipient should be considered as Rh

negative, while donors should be regarded as

Rh positive

Weakened Expression of the D Antigen

Some red blood cells exhibit a weakened form

of the D antigen (formerly known as Du)

Red cells having weak D antigen react weakly

with anti-D reagentwith anti-D reagent

There is a quantitative reduction in the

number of D antigen sites on such red cells

Weak D donors should be considered as Rh

positive and their blood should not be

transfused to Rh-negative recipients

The C and c Antigens

C and c behave as antithetic antigens

That is, they are encoded by allelles , or

alternative forms of a gene at the same locus

Thus, on one chromosome an individual could

have a C gene or a c gene at the locus, but not have a C gene or a c gene at the locus, but not

both

The C and c genes are codominant, and if both

are present, one on each chromosome, both are

expressed

Both antigens are less immunogenic than the D

antigen

The E and e Antigens

E and e antigens, like C and c, are antithetic

Expression of the E and e gene products is

codominant

E is an effective immunogen, almost as likely E is an effective immunogen, almost as likely

to stimulate antibody production as D antigen

The e antigen is the least effective immunogen

of the five major Rh antigens

Clinical Significance of CcEe Antibodies

All Rh antibodies should be considered to

have the potential to cause hemolytic

transfusion reactions and hemolytic disease of

newbornnewborn

For transfusion to a patient with an Rh

antibody, antigen-negative blood should be

provided wherever possible

Anti-c is clinically the most important Rh

antigen after anti-D

Anti-C, -E and e rarely cause HDN

When they do the disease is generally (but not

always) mild

D deletion

In very rare cases, people may inherit Rh gene

complexes lacking alleles at the Ee locus or at the

Ee and Cc loci

These are called D deletion genes

People with these phenotypes are detected only People with these phenotypes are detected only

when they are homozygous for the rare deletion

genotype, have two different deletion genotypes

(one on each chromosome) or are part of the

family study of a person who meets either of the

previous two criteria

D deletion blood is characterized by increases

in the number of D antigen sites on the red

blood cell, resulting in stronger reactions with

anti-D antisera than cells having no deletionsanti-D antisera than cells having no deletions

Rhnull

Red blood cells that carry no Rh system

antigens at all

Rhnull individuals who have been transfused or

who are pregnant may form Rh system who are pregnant may form Rh system

antibodies

The serum of the people who form these

antibodies agglutinates cells from all people

except another Rhnull

The Rh system antigens have been shown to

be an integral part of the red blood cell

membrane lipid bilayer

The total absence of Rh system antigens

results in a hemolytic anemia due to the

resulting defect in the red blood cell resulting defect in the red blood cell

membrane

This hemolytic anemia is due to increased

destruction of red blood cells in the spleen

and is usually compensated by increased red

blood cell production in the bone marrow

Rhnull people may have a slightly decreased

hemoglobin and hematocrit

However, the anemia is usually not severe

enough to cause significant reduction in enough to cause significant reduction in

oxygen-carrying capacity

Rh System Antibodies

Usually red blood cell-stimulated

Immunization occurs when the individual

receives red blood cells carrying Rh antigens

not present on his or her own cells either not present on his or her own cells either

through a transfusion or during pregnancy and

is thus sensitized to that antigen

Most Rh antibodies are of the IgG class

IgG antibodies may occur in mixtures with a

minor component of IgM

The antibodies usually appear between 6

weeks and 6 months after exposure to the Rh

antigen

In practice, Rh antibodies can cause hemolytic

transfusion reaction or hemolytic disease of

newborn newborn

Due to high immunogenicity of D antigen, Rh-

negative persons, especially women of child

bearing age, should be transfused only with

Rh-negative blood

During pregnancy, IgG anti-D can cross the

placenta and induce hemolytic disease of

newborn by causing immune hemolysis of

fetal red cellsfetal red cells

Anti-D and anti-c can cause severe hemolytic

disease of newborn (HDN)

Anti-C, anti-E and anti-e usually do not cause

HDN or cause mild HDN

IgG Rh system antibodies react best at 37C

and are enhanced when tested against

enzyme-treated red blood cells