Rh Blood Group System

1
Rh Blood Group System

• Renee Newman Wilkins, Ph.D., MLS(ASCP)CM
• CLS 325/435
• School of Health Related Professions
• University of Mississippi Medical Center

2
Basic Objectives

• List the major antigens in the Rh system
• Use Fisher-Race, Wiener and Rosenfield
  nomenclature for the Rh system
• Explain basic Rh genetics
• Discuss how to detect the D antigen
• Define weak D and list the causes of this
  phenotype
• Discuss the characteristics of Rh antibodies

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Rh blood group system

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

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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

5
History

• 1939 Levine and Stetson defined D antigen (Rh
  factor)
• 1940 Landsteiner and Weiner discovered anti-Rh
  (named after Rhesus monkey)
• Agglutinated 85 human RBCs
• 15 RBCs did not agglutinate
• The antibody was similar to guinea pig and rabbit
  antibodies produced when stimulated with rhesus
  monkey RBCs
• Although they were later shown to be different,
  the name remained

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History

• Discovery of the Rh system
• Levine and Stetson linked the Rh factor to HDN
• Weiner linked Rh factor to transfusion reactions

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Rh Antigen Frequency

• D antigen 85
• C antigen 70
• c antigen 80
• E antigen 30
• e antigen 98

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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

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Proteins
RHD gene
RHCE gene
Chromosome 1
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Rh Nomenclature

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

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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)

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

• There are 8 gene complexes at the Rh locus
• Fisher-Race uses DCE as the order
• Others alphabetize the genes as CDE

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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

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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)

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

• 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

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Wiener Genes and Antigens
Blaney Howard (2009) Basic and Applied Concepts
of Immunohematology
Sometimes d is written just to indicate that D
is absent
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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
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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
• Usually, this can be written in shorthand,
  leaving out the h
• DCe is written as R1

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Who was right?

• Both Fisher-Race and Weiner were on the right
  track
• Molecular genetics has shown that both theories
  were partially right
• Weiner theorized that the genes have multiple
  specificities
• Fisher-Race theorized that there were more than
  one gene (3 to be exact!)

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Rosenfield Nomenclature

• Antigens are designated by number
• Rh1D
• Rh2C
• Rh3E
• Rh4c
• Rh5e
• Example
• D, C, E-, c, e is written as
  Rh1,2,-3,4,5

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ISBT

• International Society of Blood Transfusion (ISBT)
• Attempts to standardize nomenclature
• Six digit numbers are assigned to each blood
  group specificity
• 004 refers to the Rh system
• The remainder is the Rosenfield system number
  (i.e. C antigen is RH2)
• Example ISBT for the C antigen is 004002

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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

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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
• Refer to Table 5-4 in Blaney Howard if needed

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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