Rhesus blood

group System
LILIAN ANTWI BOATENG
DEPARTMENT OF MEDICAL LAB. TECH.
KNUST

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 OUTLINE
• Overview of blood group system (ABO)
• What is the rhesus system
• History of its discovery
• Mode of inheritance
• Antigenes (Genes) of the Rh system
• Nomenclature
1. Weiner
2. Fischer
• Rhesus incompatibility
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 REVISION
•What do you know
about the blood
group system
(2 year)
nd

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 History of the Rh system
• Before the 20th Century, blood and its functions
was poorly understood

• During blood loss, doctors transfused blood

from either human or animals to injured
patients

• This sometimes helped to revive the patients

and in many more cases, it was detrimental

• No one could determine what reaction actually

took place during blood transfusion
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• In 1900, Karl Landsteiner discovered the
A,B,AB,O blood group which helped to explain
the phenomenon
• In 1940, Landsteiner and his colleagues further
discovered another blood group antigen during
their studies on the rhesus monkey
• They found that blood from the monkey clotted
when injected into guinea pigs and rabbits
• This was because of the presence of another
blood group antigen that had not been
previously classified
• Landsteiner named this antigen as Rh (Rhesus
factor)
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 What is the rhesus system
• Also known as Rh factor or rhesus factor

• They are antigens on the surface of the red blood

cell of most people

• They are determined by two genes, RHD and RHCE,

which are located on chromosome 1

• An individual with the D antigen is termed as Rh ‘D’

Positive

• An individual that lacks the D antigen is termed Rh

‘D’ Negative
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• The Rh system is composed of about 49 antigens

• But the C, c, D, d, E, e are most commonly

identified and clinically important in transfusion.

• However D is the most immunogenic and commonly

involved in most Rh incompatibilities
D>c>E>C>e
Highly Rarely

• Antibodies to CcEe antigens are rare however

there have been instances that adverse reactions
have occurred requiring treatment

• An individual is thus mostly termed as Rh ‘D’

positive or Rh ‘D’ Negative
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• Percentage of Rh positive and negative
varies with race (85% of Americans are
Rh positive, while 90-95% of African
Americans are also positive?

• What percentage of black Africans are

Rh positive?????????????

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 Antigens of the Rh system &
their Mode of inheritance
• Researchers further established that the Rh
factor like the ABO is also inherited.

• An individual inheriting the RhD gene

produces the D antigen and the RhCE gene
produces C, c and E, e

• RHCE exists in four allelic forms and each

allele determines the expression of two
antigens in Ce, ce, cE or CE combination
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• The C/c antigen polymorphism appears to be
associated with four amino acid substitutions,

• whereas the E/e polymorphism is associated

with a single amino acid substitution

• An individual inherits three sets of Rh genes

from each parent called a haplotype (ie.
CcDdEe)

• Meaning we possess two of each gene which

can be passed on to our offsprings

• A person possessing one or more of rh positive

genes(C,D,E) anywhere in their haplotype is
Rh positive (eg. cDe/cdE, Cde/cDe) 10
 Antigen expressed position
C c
cysteine tryptophan 16 1
isoleucine leucine 60
serine asparagine 68 2
Serine proline 103

E e
proline alanine 226
.

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• The antigens are well developed before
birth ( 6 weeks old foetus)

• They are fully expressed on cord blood

• Rh antigens have not been demonstrated

on platelets, leucocytes, saliva and
amniotic fluid
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 Rh Null phenotype
• Red cells have no Rh antigen sites
• Genotype written ---/---
• The lack of antigens causes the red cell
membrane to appear abnormal leading to:
– Stomatocytosis
– Hemolytic anemia

– Such individuals have defective cation

transport across the red cell membrane.

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• 2 types:
– Regulator type – gene inherited, but not
expressed
– Amorph type – RHD gene is absent, no
expression of RHCE gene

• Complex antibodies may be produced

requiring use of rare, autologous or
compatible blood from siblings

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 Nomenclature of the Rh blood
group system
• Terminology used to describe the Rh system is
derived from 4 set of investigators
•
• Two of the terminologies are based on the postulated
genetic mechanisms of the Rh system.

• 3rd terminology describes only the presence or

absence of a given antigen.

• 4th is result of the effort of the International

Society of Blood Transfusion (ISBT) Working Party
on Terminology for Red cell Surface antigens.

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 Fischer-Race Terminology
(DCE Terminology)
• They postulated that the antigens from
the system were
produced by 3 closely linked sets of alleles.
Each gene was responsible for producing a
product (Ag) on the red cell surface.
• He proposed that each person inherits a
set of genes from each parent (D,C, E
genes for D, C,c and E,e antigens
respectively
• The genes are co-dominant and express
their corresponding antigen on the red cell
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• Combination of both maternal and paternal
haplotype determines the genotype of an
individual

• Fisher and Race named the antigens of the

system D, d, C, c, E, and e

• For eg. Cde haplotype from mother and

cDE haplotype from father or vice versa
gives Cde/cDE (genotype)

• According to Fischer-Race, it is reported

as DCE because he postulated that the
C/c locus lies between the D/d and E/e
loci
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 Weiner Terminology
• According to Weiner, the gene responsible
for defining Rh actually produced an
agglutinogen (a substance that stimulates
the production of an agglutinin, thereby
acting as an antigen) that contained a series
of blood factors.
• Each agglutinogen has 3 factors
• The three factors are the antigens
expressed on the cell.
– For example the agglutinogen R0= D, c, e

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• Each factor is an antigen recognized by
an antibody.

• The agglutinogen may be considered the

phenotypic expression of the haplotype.

• C,c,E,e,D represent actual antigens

recognised by specific antibodies
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• It is worth noting that Wiener’s nomenclature
represent the presence of a single haplotype
composed of three different antigens

• Weiner used R or r with 1 or 2 or ‘ or “ to

represent the set of antigens.

• R= D antigen r = absence of the D antigen (d).

• C= indicated by 1 or a single ( ′ ) c= when there

is no 1 or (′)

• E=is indicated by 2 or ( ″ ) e= there is no 2 or ( ″ )

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• Example
R1 = DCe R0 =Dce r′ =dCe

E=is indicated by 2 or ( ″ ) e= there is no 2 or

( ″)

Example
R2=DcE r″ =dcE

When both C and E are present the letter Z or

Y is used.
RZ=DCE rY=dCE

R1r =DCe/dce r′r =dCe/dce

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• When referring to the Rh Ag (factor) in wiener
nomenclature the single prime ( ' ) refers to
either C or c.

• The double prime ( ″ ) refers to either E or e.

• If the r precedes the h ( rh′ or rh″ ) we are

referring to C or E Ags respectively.

• When the h precedes the r we are referring to

either c
• ( hr′ ) or e ( hr″ ) Ags.
Rho = D

• There is no designation for the absence of D

Ag.
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 Rhesus Antibodies
Rh antibodies are produced following exposure
of an individual immune system to foreign red
cells (through pregnancy or transfusion)

• Exposure to less than 1 ml of Rh positive red

cell is enough to stimulate the production of
Antibodies

• They are IgG, reacting optimally at 370C or

following addition of antiglobulin reagent

• Rh antibodies often persist in the circulation

for year
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 Rhesus incompatibilities
• Rh incompatibility is also known as Rh disease.
• This condition occurs when an Rh negative blood
type individual is exposed to Rh positive blood
cells leading to the production of Rh antibodies.

• It usually occurs by 2 mechanisms

1. When an Rh-negative pregnant mother is
exposed to Rh-positive fetal red blood
cells

2. When an Rh-negative female receives an

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• Fetal cells may cross the placenta to the
maternal blood through:
Spontaneous or induced abortion,
Trauma
Invasive obstetric procedures
Normal delivery
• After significant sensitization, the mother
produces Rh antibodies which are capable of
freely crossing the placenta to the foetal
circulation
• They form antigen-antibody complex with the
Rh positive fetal cells and eventually destroy
them causing fetal alloimmune-induced
hemolytic anaemia
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 Rh D antigen
• The most immunogenic of the Rh antigens
• It is shown to contain about 30 different
epitopes (using monoclonal antibody testing)

• Some individuals lack some epitopes and are

thus classified as partial D

• Such individuals may be stimulated to produce

antibodies to the missing epitopes through
transfusion or pregnancy
• The antigens were designated Droman numeral
• DvI is the clinically most important partial D
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 Weakened Expression of D

• Not all D positive cells react equally well

with anti-D.
• RBCs not immediately agglutinated by
anti-D must be tested for weak D.
• Causes
– Genetic
– Position effect
– Mosaic
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 Weak D Genetic

• An individual inherits a D gene that codes

for less D antigens on the RBC

• The D Ag expressed appear to be complete

but few in number

• most frequently in black.

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 Weak D - Genetic

RBC with Weak D (Du)

normal
amounts of D
antigen
 Position Effect
• C trans - position effect;

• The D gene is in trans to the C gene, eg., C and D

are on OPPOSITE sides: Dce/dCe

• C and D antigen arrangement causes steric

hindrance which results in weakening or
suppression of D expression.
 Position Effect

C in trans position to D:

Dce/dCe Weak D

C in cis position to D:

DCe/dce NO weak D
 Partial D
• Absence of a portion or portions of the total
material that comprises the D antigen.
• Known as “partial D” (old term “D mosaic”).
 D Mosaic/Partial D
• If the patient is transfused with D
positive red cells, they may develop an
anti-D alloantibody* to the part of the
antigen (epitope) that is missing
Missing
portion

RBC RBC

*alloantibody- antibody produced with specificity other than self

 Summary -Rh D
• Weak D patients should be treated as
Rh D positive.
• Partial D patients should be treated as
Rh D negative.
• Weak D blood donors should be treated
as Rh D positive.
• Partial D blood donors should be treated
as Rh D positive.

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 G Antigen
– Genes that code for C or D also code for G

– Detected on cells that express the D or C

antigens or both

– G almost invariably present on RBCs

possessing C or D

– Anti-G mimics anti-C and anti-D.

– Anti-G activity cannot be separated into

anti-C and anti-D.
 assignment

• Read and Discuss the different types of

the D antigen

Submission date: 7th Feb, 2013

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 References
• Salem L, Dyne PL, Rh Incompatibility

• Daniels, G. (2002). Human Blood Groups

2nd Ed. Blackwell Science Ltd.

• Hoffbrand AV, Petit JE (1993)

Essential Haematology, 3rd Edition,
Blackwell Scientific Publications, London
Edinburgh
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 Thanks for
listening

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