Transcript Rh antibodies

Lecture 4 bb
The Rhesus (Rh) Blood Group system
By Dr. Dalia Galal Hamouda
The Rh(D) Antigen
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Rh is the most complex system, with over 45 antigens.
The complexity of the Rh blood group Ags is due to the
highly polymorphic genes that encode them.
Discovered in 1940 after work on Rhesus monkeys.
The 2nd most important after ABO in the cross-match test.
Rh Genetics
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The genes that control the system are autosomal
codominant located on the short arm of
chromosome 1.
The RhD gene encoding the D antigen is the most
important which is a large protein on the red blood
cell membrane
Rh Antigen Frequency
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D antigen – 85%
d antigen – 15%
C antigen – 70%
c antigen – 80%
E antigen – 30%
e antigen – 98%
Rh Positive
Rh Negative
The presence or absence of D Ag determines if the person is
Rh+ or Rh-
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Rh antigens are highly immunogenic, the D
antigen is most potent
D  c E  C  e
Highly
Rarely
Immunogenic
Exposure to less than 1 ml of Rh positive red
cells can stimulate Ab production in an Rh
negative person.
Nomenclature of the RH system
3 Different nomenclatures:
1- Fisher-Race
2- Weiner
3- Rosenfield Nomenclature
1- Fisher-Race Theory
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Rh inheritance is controlled by 3 closely linked loci on
each chromosome.(crossing over does NOT occur) and
the 3 genes on one chromosome are always inherited
together
Each locus has its own set of alleles which are: Dd , Cc ,
and Ee .
The D gene is dominant to the d gene, but Cc and Ee are
co-dominant.
Fisher-Race Example:
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DCe/DCe individual is homozygous for D, C, and
e genes
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DCe/dcE individual is heterozygous for D, C, e,
d, c, and E genes
2- Wiener Theory
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There is one Rh locus at which occurs one Rh gene, but
this gene has multiple alleles.
For example, one gene R1 produces one agglutinogen
(antigen) Rh1 which is composed of three "factors"
The three factors are analogous to C, D, and e respectively
The main difference between the Fisher-Race and Wiener
theories is that the:
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Fisher-Race theory has three closely linked loci,
the Wiener theory has only one gene locus at which multiple
alleles occur.
3- Rosenfield Nomenclature
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Each antigen assigned a number
Rh 1 = D
Rh 2 = C
Rh 3 = E
Rh 4 = c
Rh 5 = e
In writing the phenotype, the prefix “Rh” is followed by colon, then number
(if negative, number is preceded by -)
Example: D+, C+, E-, c+, e+ is written as
Rh:1,2,-3,4,5
Significance of Rh system
After ABO, the Rh system is the second most important system.
This is because:
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The D antigen is extremely immunogenic (activate the antibody
production).
It causes the production of anti-D in 50 - 70% of Rh(D) negative
people who are exposed to the D antigen.
Anti-D is the most common cause of severe hemolytic disease of
newborn (HDN) and can cause in Utero death.
Because of this, in blood transfusion, the patient and donor must be
matched for Rh(D) type as well as ABO groups.
The C and E Ags are not as immunogenic as D, routine typing for
these Ags is not performed
Rh antibodies
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Result from the exposure to Rh antigens
IgG form
Bind at 37°C and form agglutination
Clinical important of Rh antibodies
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Related to Hemolytic and transfusion reactions
Re-exposure to antigen cause rapid secondary response
If any donor blood sample that types Rho(D) negative by either slide or
rapid method must be tested further by indirect anti-globulin test
(IDAT).
If both test results are negative, the donor sample is considered Rh
negative
Hemolytic disease of the Newborn (HDN)
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Usually related to D antigen exposure and the formation of
anti-D
Usually results from D negative female and D positive male.
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The baby will probably be D positive.
1st pregnancy not effected, the 2nd pregnancy and on will be
effected-results in still birth, severe jaundice, anemia related
to HDN.
To prevent this occurrence the female is administered RHimmunoglobulin (IG).
Rh factor
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Rh factor can cause
complications in some
pregnancies.
Mother is exposed to Rh
antigens at the birth of
her Rh+ baby.
First pregnancy
Placenta
Rh+ antigens
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Mother makes anti-Rh+
antibodies.
Anti-Rh+
antibodies
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During the mother’s next
pregnancy, Rh
antibodies can cross the
placenta and endanger
the fetus.
Possible
subsequent
pregnancies
Weak D Phenotype
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Most D positive rbc’s react macroscopically with Reagent
anti-D at immediate spin
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These patients are referred to as Rh positive
Reacting from 1+ to 3+ or greater
HOWEVER, some D-positive rbc’s DO NOT react (do
NOT agglutinate) at Immediate Spin using Reagent Anti-D.
These require further testing (37oC and/or AHG) to
determine the D status of the patient.