The term Rhesus system refers to all of the antigens of the Rhesus blood group system - the five main rhesus antigens (C,c,D,E and e) as well as many other less frequent antigens. The terms Rhesus factor and Rh factor are equivalent and refer to the Rh D antigen only.
Rhesus factor
Individuals either have, or do not have, the
Rhesus factor (or Rh D antigen) on the surface of their
red blood cells. This can be indicated with a plus (+) or minus (−) suffix after the
ABO blood type (ie A- or O+), but for clarity in laboratory work it is better not to use this notation, which could be changed by a smudge. For laboratory work the suffixes 'Rh D positive', 'RhD pos', 'D pos' or 'RhD pos' may be used for Rhesus D positive blood, and the suffixes 'Rh D negative', 'RhD neg', 'D neg' or 'RhD neg' may be used for Rhesus D negative blood.
History of discovery
The Rhesus system is named after the
Rhesus monkey, following experiments by
Karl Landsteiner and
Alexander S. Wiener, which showed that rabbits, when immunised with rhesus monkey red cells, produce an antibody that also
agglutinates the
red blood cells of many humans. Landsteiner and
Alexander S. Wiener discovered this factor in 1937 (publishing in 1940).
[Landsteiner K, Wiener AS. An agglutinable factor in human blood recognized by immune sera for rhesus blood. Proc Soc Exp Biol Med 1940;43:223-224.] The significance of the Rh factor was soon realized.
Dr. Phillip Levine made a connection betwen the Rh factor and the incidence of
erythroblastosis fetalis, and Wiener realized adverse reactions from tranfusions were also resulting from the Rh factor. Wiener then pioneered the "exchange transfusion" to combat
erythroblastosis fetalis in newborn infants. This transfusion technique saved the lives of many thousands of infants before intrauterine transfusion was invented which enabled much more severely affected fetuses to be successfully treated.
Rh nomenclature
The Rhesus sytem has two sets of nomenclatures, one developed by Drs. Fisher and Race and one by Dr. Wiener. Both systems reflected alternate theories of inheritance. The Fisher-Race system, which is more commonly in use today, utilizes the CDE nomenclature. This system originally postulated that there are three closely linked genes on each chromosome. The genes were designated as D and its hypothetical allele d; C and its allele c, E and its allele e. Each gene was supposed to control the product of the corresponding antigen (i.e., D gene produces D antigen, etc.) However, the d gene was hypothetical, not actual.
The Wiener system used the Rh-Hr nomerclature. This system theorized that there was one gene at a single locus on each chromosome of the of the pair which controls production of multiple antigens. This concept postulated that a gene R gives rise to the “blood factors” Rho, rh’, and hr” and the gene r will reduce hr’ and hr”.
Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D)). Wiener’s notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher-Race theory is more widely used.
DNA testing has shown that both theories are partially correct. There are in fact two linked genes, one with multiple specificities and one with a single specificity. Thus, Wiener's postulate that a gene could have multiple specificities (something many did not give credance to originally) has been proven correct. On the other hand, Wiener's theory that there is one gene has proven incorrect, as has the Fischer-Race theory that there are three genes.
The Rhesus system antigens
The proteins which carry the Rhesus antigens are transmembrane proteins, whose structure suggest that they are
ion channels. The main antigens are C, D, E, c and e, which are encoded by two gene loci, the
D locus and the
CE locus. There is no d antigen. Lowercase "d" indicates the absence of the D antigen (the gene is either deleted or nonfunctional).
Rhesus genotypes
| Genotype
| symbol
| Rh(D) status
|
| cde/cde | rr | Negative
|
| CDe/cde | R1r | Positive
|
| CDe/CDe | R1R1 | Positive
|
| cDE/cde | R2r | Positive
|
| CDe/cDE | R1R2 | Positive
|
| cDE/cDE | R2R2 | Positive
|
Hemolytic disease of the newborn
RhD Hemolytic disease of the newborn is often called Rhesus disease or Rh disease for brevity. Sensitization to Rh D antigens (usually by feto-maternal transfusion during pregnancy) may lead to the production IgG anti-RhD antibodies which can pass through the placenta. This is of particular importance to RhD negative females of or below childbearing age, because any subsequent pregnancy may be affected by the Rhesus D hemolytic disease of the newborn if the baby is Rh D positive. The vast majority of Rh disease is preventable in modern antenatal care by injections of IgG anti-D antibodies (Rho(D) Immune Globulin),
Rhc antigens can occasionally cause a severe hemolytic disease of the newborn (anti-Rhc).
Population data
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
Population
| Rh(D) Neg
| Rh(D) Pos
| Rh(D) Neg alleles
|
| European Basque
| approx 35%
| 65%
| approx 60%
|
| Caucasian
| 16%
| 84%
| 40%
|
| American Blacks
| approx 7%
| 93%
| approx 26%
|
| Native American Indians
| approx 1%
| 99%
| approx 10%
|
| African descent
| less 1%
| over 99%
| 3%
|
| Japanese & Chinese
| less 1%
| over 99%
| 1%
|
Inheritance
The Rh(D) antigen is inherited on one locus (on the short arm of the
first chromosome, 1p36.13-p34.3) with two alleles, of which Rh+ is dominant and Rh− recessive. The gene codes for a
polypeptide on the red cell membrane. Rh− individuals (
dd genotype) do not produce this antigen, and may be sensitized to Rh+ blood.
Two very similar epitopes, Cc and Ee, appear to be closely related to Rh.
References
- Mollison PL, Engelfriet CP and Contreras M. Blood Transfusion in Clinical Medicine. 1997. 10th edition. Blackwell Science, Oxford, UK.
Blood | Blood antigen systems
Rhesusfaktor | Factor Rh | Groupe Rhésus | Rezus faktorius | Rhesusfactor | Rh因子 | Rh | Factor Rh