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Rhesus Blood Group System

How, when, and by whom was the system discovered?
Rhesus (Rh) blood group system was discovered in 1940 by Karl Landsteiner
and Alexander Wiener. This was 40 years after Landsteiner had discovered the
ABO blood groups. Over the last half century, we have learned far more about
the processes responsible for Rh types. This blood group may be the most
complex genetically of all blood type systems since it involves 45 different
antigens on the surface of red cells that are controlled by 2 closely linked genes
on chromosome1.
D (Rho) is the most important antigen after A and B antigens. Unlike the anti-A
and anti-B antibodies, anti-D antibodies are only seen if a patient lacking D
antigen is exposed to D + cells. The exposure of D+ cells usually occurs through
pregnancy or transfusion.
There are at over 40 Rh antigens that have been identified including those that
are either combinations of these antigens or weak expressions of the above
antigens, but most Rh problems are due to D, C, E, c or e.

How many loci are there and on what chromosome?

There are three genetic loci on chromosome 1. They are closely linked and
are referred to as C, c, D, e and E loci.
How many alleles are there for each locus?
There are three closely linked sets of alleles with little or no crossing
over between loci.
Five major antigens (D, C, E, c, and e).

• D is inherited at one locus

• C or c at the second locus
• E or e at the third locus

Statistics about occurrence of genes in the population. Are there any

statistics for the UAE?
The frequency of Rh factor blood types and the RhD neg allele gene differs in
various populations.

Population data for the Rh D factor and the RhD neg allele

Rh(D) Neg
Population Rh(D) Neg Rh(D) Pos
European Basque approx 35% 65% approx 60%

Caucasian 16% 84% 40%

American Blacks approx 7% 93% approx 26%

Native Americans approx 1% 99% approx 10%

African descent less 1% over 99% 3%

Asian less 1% over 99% 1%

What types of antibodies are produced? IgG? IgM? Both?

IgG class - react best at 37 ºC - indirect antiglobulin technique
Can the system be the cause of a HTR (Hemolytic Transfusion Reaction)
or HDNB (Hemolytic Disease of the Newborn)?
All Rh antibodies can cause severe transfusion reaction and Haemolytic
Disease of the Newborn (H.D.N.B). Rh incompatibility is the most
common and severe cause of HDN. This incompatibility may occur
when an Rh-negative mother and an Rh-positive father have an Rh-
positive baby. Cells from the baby can cross the placenta and enter the
mother's bloodstream, causing the mother to make anti-D antibodies.
Unlike ABO antibodies, the structure of anti-D antibodies makes it likely
that they will cross the placenta and enter the baby's bloodstream.
There, they can destroy the baby's red blood cells, causing a severe or
fatal anemia.

Is there any other information specific for the system?

Rh Antigens:
The Rh antigens together are proteins of 417 amino acids. These proteins cross
the red cell membrane 12 times. There are only small loops of the protein on the
exterior of the cell membrane.
Therefore the Rh antigens are not as available to react with their specific
antibodies and there are fewer antigen sites than ABO. Unlike the ABO system
the Rh antigens are not soluble and are not expressed on the tissues.

Rh Antibodies:
Unlike the ABO antibodies that are mainly IgM, the Rh antibodies are commonly
IgG. They are NOT naturally occurring and therefore are formed by immune
stimulus due to transfusions or baby's red blood cells during pregnancy. The
most common antibody to form is anti-D in Rh negative individuals.
Rh antibodies will react more strongly with homozygous cells than with
heterozygous cells. For example, an anti-E will react with strongly with E+E+
cells and more weakly with E+e+ cells. This is called dosage.