blood group sytem

1. www.gmu.ac.ae College of Health Sciences
July 24, 2023
LS-IBB 201 – Lecture 4
Rh blood group system
Dr.Ayman Hussein Mohamed Ahmed Al-feel
Assistant Professor of Hematology & Blood Bank
Medical Laboratory Sciences program,
College of Health Sciences,
Gulf Medical University

2. outline:
- Historical Overview of of Rh blood system
- Importance of RH system
- Nomenclatures of Rh system
- Antigens of the Rh Blood group system
- Major Rh Blood Group
- Rh Antibodies
- Clinical significance of Rh
- LW Blood Group System

3. History:
In 1939 Levine and Stetson described a hemolytic transfusion reaction in an
obstetric patient following delivery of still born infant. The women required
transfusion. Her husband, who had the same ABO type, was selected as her donor,
after transfusion the recipient, demonstrated the classic symptoms of acute
hemolytic transfusion reaction.
In 1940 Landsteiner and Wiener showed that antibodies produced against the
rhesus monkey RBCs agglutinated RBCs of 85% of a human population.
• The antibody was similar to guinea pig and rabbit antibodies produced when
stimulated with rhesus monkey RBCs
• Natural antibodies against the Rh antigens do not occur.
• Discovery of the Rh system:
• Levine and Stetson linked the Rh factor to HDN
• Weiner linked Rh factor to transfusion reactions

4. Rh blood group system
• Consists of over 50 related antigens
• The genes that control the system are autosomal co dominant
(chromosome 1)
• Polymorphic (more than 1 phenotype)
• Only the most clinically significant will be discussed:
• D, C, E, c, and e

5. Importance of the Rh system
• After the A and B antigens, the D antigen is the most
important red cell antigen in blood banking
• The D antibody can cause transfusion reactions and
hemolytic disease of the newborn (HDN)
/Erythroblastosis fetalis

6. Rh Antigen Frequency
• D antigen – 85%
• C antigen – 70%
• c antigen – 80%
• E antigen – 30%
• e antigen – 98%
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 a Rh-negative person.

7. Rh Genetics
• 2 closely linked genes control the expression of ALL Rh
antigens (codominant alleles)
• RHD gene - determines the expression of the D antigen
• RHCE gene - determines the expression of the C, c, E, and e antigens

8. RHD gene RHCE gene
Chromosome 1
Proteins

9. Rh Nomenclature
• There are several different systems of nomenclature that
theorize the inheritance of the Rh system
• Fisher-Race
• Wiener
• Rosenfield

10. 1- Fisher-Race Nomenclature
• CDE terminology
• Most commonly used (i.e. WHO)
• Developed by Ronald Fisher and Robert Race of
England
• They theorized that the Rh antigens are controlled by a
complex of 3 sets of genes with closely linked loci (i.e.
Dce gene complex codes for D, c, e antigens)

11. Fisher-Race
D
d
C
c
E
e
3 closely linked
genes
“d” antigen not
produced
Produces D antigen
Produces C/c antigen
Produces E/e antigen

12.  3 closely linked sets of alleles.
Each gene was responsible for
producing a product (Ag) on the red
cell surface.
DCe dCe
DcE dCE
Dce dcE
DCE dce
Fisher-Race
Fisher-Race Example:
• DCe/DCe individual is homozygous for D, C, and e genes
• DCe/dcE individual is heterozygous for D, C, e, d, c, and E genes

13. 2- Wiener Nomenclature
• Rh-Hr terminology
• Rarely used, but good for describing phenotype
• A single gene at the Rh locus leads to the expression of the Rh
antigens (next slide)
• Each parent contributes 1 Rh gene
• 8 alleles exist at each gene locus
• Each gene controls production of an agglutinogen composed of
three factors (antigens)

14. Wiener Theory
Single gene at Rh
locus
rh’
hr’
Rh0
rh”
hr”
Rh0 D
rh’ C
rh” E
hr’ c
hr” e
5 Major Rh
Factors/Antigens:
(longhand version)
Produces
D antigen
on RBC
Produces C
antigen on
RBC

15. • Wiener further theorized that 8 major genes led to different
combinations of antigens (D, C, E, c, e):
• Rh0, Rh1, Rh2, Rhz
• rh, rh’, rh”, rhy
Wiener Theory

16. Wiener Genes and Antigens
Gene Antigens Gene Antigens
Rh0 Dce rh dce
Rh1 DCe rh’ dCe
Rh2 DcE rh” dcE
Rhz DCE rhy dCE
Blaney & Howard (2009) Basic and Applied Concepts of Immunohematology
Sometimes “d” is written just
to indicate that D is absent

17. Converting Wiener into Fisher-Race or vice versa
R  D
r  no D
1 and ‘  C
2 and “  E
Example: DcE  R2
r”  dcE
Written in shorthand
Differentiating superscript from subscript
• Superscripts (Rh1) refer to genes
• Subscripts (Rh1) refer to the agglutinogen (complex of antigens)
• For example, the Rh1 gene codes for the Rh1 agglutinogen made of D, C, e

18. 3- Rosenfield Nomenclature
• Antigens are designated by number
• Rh1:D
• Rh2:C
• Rh3:E
• Rh4:c
• Rh5:e
• Example
• D+, C+, E-, c+, e+ is written as Rh:1,2,-3,4,5

19. Genotype vs. Phenotype
• The phenotype is the result of the reaction between the red
cells and antisera
• The genotype is the genetic makeup and can be predicted
using the phenotype and by considering the race of an
individual
• Only family studies can determine the true genotype

20. Phenotype
• Anti-D, anti-C, anti-E, anti-c, and anti-e is tested with patient RBCs
• If a specimen gives the following reaction: D+, C+, E-, c+, e+
• The phenotype would be DCce
• The most probable genotype would be
• White population: DCe/dce
• Black population: DCe/Dce

21. Probable genotype
• If the RBCs express both C and c or E and e, the corresponding
genes are present in the heterozygous state
• If they express only C or c, or only E or e, the person is
assumed to be homozygous for that gene

22. Du phenotype
• A weaker variant of the D antigen is termed Du and is detected only by
the antigloblin (AHG) technique.
Significance of Du
1. If transfused with Du blood an individual who has anti-D antibodies
(through previous sensitization by transfusion or pregnancy) is likely to
develop severe haemolysis.
2. A sensitized Rh-negative mother having anti-D antibodies can produce
haemolytic disease of the new born (I-IDN) in a Du-positive foetus.
3. Transfusion of Du blood to an Rh-negative individual can theoretically
produce antibodies against D or Du. However, in practice, this has not
been substantiated.
4. In theory, a Du recipient can produce antibodies to transfused D-
positive cells. This also is extremely uncommon in practice.

23. Three Mechanisms for Weak D
• Genetic
• Position effect
• Mosaic
• Results in differences from normal D expression
• Quantitative (inherited weak D or position effects)
• Qualitative (mosaic D; could produce Anti-D)

24. Weak D - Genetic
• Inheritance of D genes which result in
lowered densities of D Antigens on RBC
membranes, gene codes for less D.
Weak D (Du)
RBC with normal amounts of D antigen

25. 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

26. Position Effect
• C in trans position to D:
D c e / d C e.............weak D
C in cis position to D:
D C e / d c e.......... No weak D

27. 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”).

28. D Deletion
• Very rare
• Individuals inherit Rh gene complex lacking alleles.
• May be at Ee or Cc
• Must be homozygous for rare deletion to be detected.
• No reaction when RBCs are tested with anti-E, anti-e,
anti-C or anti-c
• Requires transfusion of other D-deletion red cells,
because these individuals may produce antibodies with
single or separate specificities.
• Written as D- - or -D-

29. Rh Null
• 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
• 2 Rh null phenotypes:
• 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.

30. LW
• Discovered at same time as Rh antigen.
• LW detected on cells of Rhesus monkeys and human
rbcs in same proportion as D antigen.
• Thought was the same antigen but discovered
differences.
• Named LW in honor of Landsteiner and Wiener.
• Rare individuals lack LW yet have normal Rh antigens.
• Can form allo anti-LW.
• Reacts more strongly with D pos than D neg cells.

31. Cw
• Variant Rh antigen
• Low frequency antigen found in only 1-2% of Whites and rare in Blacks
• Most individuals who are C+ are Cw+
• Antibodies to these antigens can be naturally occuring and may play a role
in HDN and HTR

32. Rh Antibodies
• Except for rare examples of anti-E and anti-Cw which
may be naturally occurring, most occur from
immunization due to transfusion or pregnancy.
• Associated with HTR and HDN.
• Characteristics
• IgG but may have MINOR IgM component so will
NOT react in saline suspended cells (IS).
• May be detected at 37C but most frequently
detected by IAT.
• Enhanced by testing with enzyme treated cells.
• Order of immunogenicity: D > c > E > C > e
• Do not bind complement, extra vascular destruction

33. Rh Antibodies
• Anti-E most frequently encountered antibody followed by anti-c.
• Anti-C rare as single antibody.
• Anti-e rarely encountered as only 2% of the population is antigen negative.
• Detectable antibody persists for many years and sometimes for life.
• Anti-D may react more strongly with R2R2 cells than R1R1 due to higher
density of D antigen on cells

34. Thanks

35. www.gmu.ac.ae
DISCLAMER
The contents of this presentation, can be used only for the
purpose of a Lecture, Scientific meeting or Research
presentation at Gulf Medical University, Ajman.