RH Blood Group II

HEM 2133
Immunohaematology 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 Rhpositive 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)
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 RhABCD
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
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
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
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 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
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
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
newborn
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
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 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
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
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
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
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
Due to high immunogenicity of D antigen, Rhnegative 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 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

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HEM 2133

The Rh (D) Antigen

For example a person lacking RhA would be

Tippett and Sanger decribe six categories of D

Individuals with DVI variant are able to

Weakened Expression of the D Antigen

The C and c Antigens

The E and e Antigens

Clinical Significance of CcEe Antibodies

Anti-C, -E and e rarely cause HDN

D deletion blood is characterized by increases

The Rh system antigens have been shown to

Rhnull people may have a slightly decreased

The antibodies usually appear between 6

During pregnancy, IgG anti-D can cross the

IgG Rh system antibodies react best at 37C

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