Rhesus factor

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Blood group polypeptide Rh (D), Rhesus-D antigen
Properties of human protein
Mass / length primary structure 417 amino acids
Isoforms Long, short 1, short 2
Gene name RHD
External IDs
Homology family Rhesus antigen
Parent taxon Chordates

Blood group polypeptide Rh (CE), Rhesus-C / E antigen
Properties of human protein
Mass / length primary structure 417 amino acids
Gene name RHCE
External IDs
Homology family Rhesus antigen
Parent taxon Chordates

The name rhesus factor comes from the use of erythrocytes from the blood of rhesus monkeys to obtain the first test sera .

The Rhesus factors are a 1940 by Karl Landsteiner and Wiener Alexander Solomon found erythrocytes - antigen system. Rhesus-positive individuals have special proteins on the cell membrane of the erythrocytes (red blood cells), Rhesus-negative individuals do not. The name comes from the extraction of the first test serum from the blood of rabbits that had been treated with erythrocytes from rhesus monkeys ( Macaca mulatta ).

The Rhesus blood group system or Rhesus system called the - after the AB0 system - second most important blood group system of man. It consists of a group of 50 similar proteins , the five most important representatives of which (C, c, D, E, e) can be checked with test sera . The oldest and most important rhesus factor has the abbreviation D in the rhesus system:

  • If a person possesses the Rhesus factor D antigen , they are Rhesus positive and you write “Rh (D) +”, “Rh +”, “Rh” or - depending on the genotype - “Dd”, “dD”, “ DD ”, rarely also“ RH1 ”.
  • If a person does not have an Rhesus factor D antigen, they are negative for rhesus and are written as “Rh (D) -”, “Rh−”, “rh” or “dd”.

The affiliation of a person to the five most important factors C, c, D, E, e is referred to as the rhesus formula and represented as ccD.Ee or ccddee etc., see sections Inheritance patterns and the rhesus system .

About 85% of the white European and American populations are rhesus positive, about 15% rhesus negative. Almost 100% of all Africans, Asians and natives in North and South America are Rh-positive.

Significance for the organism

According to a study from 2009 with genetically engineered mice that lacked the rhesus gene RHCG and thus rhesus proteins, the proteins have important functions in the transport of ammonium ions (NH 4 + ) and ammonia (NH 3 ), the excretion of nitrogen-containing metabolic end products and maintenance a constant pH value in the blood. The genetically modified rodents showed a shift in blood pH to the acidic range, lower levels of nitrogenous substances in the urine and less fertile sperm in males.

Significance in pregnancy and blood transfusion

A life-threatening antigen-antibody reaction can occur with repeated blood transfusions of a Rh-negative individual with Rh-positive blood or from the second pregnancy of a Rh-negative woman with a Rh-positive child (see Rhesus incompatibility ). The rhesus-negative organism forms antibodies against the rhesus-positive erythrocytes, and hemagglutination (donor blood recipient) or hemolysis (child) occurs. The prevalence of blood group incompatibility in the western industrialized countries is 1–1.5 per 1000 pregnant women, the proportion of rhesus incompatibility is 40–80%.

Rhesus negative spread

Around 17% of Central Europeans are rhesus negative, around 4% in the eastern fringes of Europe, 25% in the Basque Country and around 15% in Switzerland. On other continents it is sometimes much lower. America , Australia and all of East Asia have no rhesus-negative natives at all .

The prevalence of people with rhesus negative blood plays an important role in determining the genetic distance between peoples. Large differences between nations in the incidence of Rhesus-negative blood indicate great genetic distance and, according to studies by Cavalli-Sforza and others, suggest an early branching of the races. The studies complement the findings that emerged from the study on lactose intolerance .

The cause of the strong variation in the RhD alleles is still unclear and, in view of the harmful effects on reproduction, had a mysterious effect. There are recently the first studies (2008/2009) that establish a connection with toxoplasmosis in humans - accordingly, RhD-heterozygous toxoplasmosis-infected people have faster physical reactions in critical situations than the two RhD-homozygous carriers, and can thus have the effect Compensate, which is modern in a higher number of traffic accidents with toxoplasmosis infection. In the absence of toxoplasmosis people without RhD allele show (homozygous negative) the best response times - the proliferation of wild cats in the African region may contain the spread of the RhD allele have greatly promoted, while in Europe the domestic cat only since ancient times in the People's living environment.

Inheritance pattern

The inheritance of the rhesus factor is dominant-recessive : the expression of the factor is dominant compared to the rhesus-negative phenotype .

In contrast to the Rh factor “D”, which was primarily discovered, the small letters for the gene products of the Rh-CE gene (the most important antigen combinations are CE, Ce, cE and ce) also stand for antigens that can be detected by test sera with appropriate antibodies . In addition to the anti-C serum, there is also an anti-c serum etc. (the same applies to the Kell system ). The Rhesus factors therefore appear to appear twice as "ccddee" on standard-compliant German blood donation cards. The possibility of combination makes the Rh blood group system one of the most complex human blood group systems.

Representation of the inheritance of the Rhesus factor. Blue the paternal line, red the maternal line.
Rh phenotypes and genotypes
Phenotype expressed in the cell Genotype expressed in the DNA Frequency (%)
Fisher-Race spelling Viennese spelling
D + C + E + c + e + (RhD +) Dce / DCE R 0 R Z 0.0125
Dce / dCE R 0 r Y 0.0003
DCe / DcE R 1 R 2 11.8648
DCe / dcE R 1 r '' 0.9992
DcE / dCe R 2 r ' 0.2775
DCE / dce R Z r 0.1893
D + C + E + c + e− (RhD +) DcE / DCE R 2 R Z 0.0687
DcE / dCE R 2 r Y 0.0014
DCE / dcE R Z r '' 0.0058
D + C + E + c− e + (RhD +) DCe / dCE R 1 r Y 0.0042
DCE / dCe R Z r ' 0.0048
DCe / DCE R 1 R Z 0.2048
D + C + E + c− e− (RhD +) DCE / DCE R Z R Z 0.0006
DCE / dCE R Z r Y <0.0001
D + C + E− c + e + (RhD +) Dce / dCe R 0 r ' 0.0505
DCe / dce R 1 r 32.6808
DCe / Dce R 1 R 0 2.1586
D + C + E− c− e + (RhD +) DCe / DCe R 1 R 1 17.6803
DCe / dCe R 1 r ' 0.8270
D + C− E + c + e + (RhD +) DcE / Dce R 2 R 0 0.7243
Dce / dcE R 0 r '' 0.0610
DcE / dce R 2 r 10.9657
D + C− E + c + e− (RhD +) DcE / DcE R 2 R 2 1.9906
DcE / dcE R 2 r '' 0.3353
D + C− E− c + e + (RhD +) Dce / Dce R 0 R 0 0.0659
Dce / dce R 0 r 1.9950
D− C + E + c + e + (RhD−) dce / dCE rr Y 0.0039
dCe / dcE r'r '' 0.0234
D− C + E + c + e− (RhD−) dcE / dCE r''r Y 0.0001
D− C + E + c− e + (RhD−) dCe / dCE r'r Y 0.0001
D− C + E + c− e− (RhD−) dCE / dCE r Y r Y <0.0001
D− C + E− c + e + (RhD−) dce / dCe rr ' 0.7644
D− C + E− c− e + (RhD−) dCe / dCe r'r ' 0.0097
D− C− E + c + e + (RhD−) dce / dcE rr '' 0.9235
D− C− E + c + e− (RhD−) dcE / dcE r``r '' 0.0141
D− C− E− c + e + (RhD−) dce / dce rr 15.1020

† The R 0 haplotype is much more common in people with roots south of the Sahara.

Rhesus system

Rhesus genotypes
genotype Rhesus type Rh (D) test
ccddee rr Rh negative
CcDdee R 1 r Rh positive
CCDDee R 1 R 1 Rh positive
ccDdEe R 2 r Rh positive
CcDDEe R 1 R 2 Rh positive
ccDDEE R 2 R 2 Rh positive

After the discovery of blood groups A and B, Landsteiner and Wiener continued their work. In the first designation by Wiener, the “R” stood for the responsible gene in rhesus monkeys, and the appended “h” for the associated antiserum. With a locus, “Rh” now stood for the positive test and “rh” for the negative test. Since other blood group characteristics were found, this designation as the Rh factor, which refers to today's Rhesus factor D (also called Rh1 or RhD), did not gain acceptance. However, due to its widespread use in specialist literature, the nickname was retained.

Fisher and Race recognized the connection between the other blood group characteristics and, in updating the known A and B of the AB0 system, introduced the designations C, D and E of the Rhesus system. Statistician Fisher and immunobiologist Race assumed three loci in the genome, each with binary expressions of the genes as C / c, D / d and E / e. Only later was it recognized that the characteristics for C and E lie on the same locus and consequently exist in four allele types. The two genes of the Rh system are on chromosome 1 at 1p36.2-p34 ( GeneID 6007 "RHD" and GeneID 6006 "RHCE" ).

Often, when specifying the D / d genes, only negative "dd" and positive, written as "D." or "D" , differentiated, the latter stands for both "DD" and "Dd" , but this differentiation is only possible through a (complex / expensive) exact genome analysis. Example: The blood donation card says ccDee or ccD.ee, the donor has ccDdee or ccDDee.

The most common
rhesus formulas
in Germany:
RH positive:
Cc D.ee 35.0%
CC D.ee 18.5%
Cc D.Ee 13.0%
cc D.Ee 11.9%
cc D.EE 2.3%
cc D.ee 2.1%
Cc D.EE <1%
RH negative:
cc dd ee 15.1%
Cc dd ee 0.76%
cc dd Ee 0.92%

Later genetic engineering investigations were able to largely confirm the previous assumptions, in which the blood groups of the Rh system are closely related. The resulting proteins of the Rhesus system are largely homologous, so that it has long been assumed that they arise through alternative splicing of a common long gene sequence, as a result of which sometimes 1, 2 or even 3 variants arise in an organism. Carritt et al. then showed in 1997 the possibility that the RhCE arose through gene duplication from RhD, especially after a missing rhesus protein appeared for the first time in the human genome. (In some distant populations there are still no RhD-negative blood groups). In contrast to the assumption of Carrit et al. Willy A. Flegel and Wagner then showed in 2000 that the RhCE was the original gene from which RhD was duplicated. In 2000, several teams also showed that the genes for RhCE and RhD are close together and in opposite reading directions (the 3 'ends are adjacent). This also explains why a whole series of rarer Rhesus characters could be found in which exons of the RhD protein appear to be expressed in the RhCE protein .

Since there are other wild types in addition to the frequent forms of the Rh-D and Rh-CE genes, there is also a numerical notation for the blood group characteristics of the Rh system in the literature. Here D = RH1, C = RH2, E = RH3, c = RH4, e = RH5, ... C w = RH8 ... with over 50 variants today. How these are actually expressed in the genome has not yet been finally clarified. Non-human model organisms such as the mouse are not fully suitable for comparison because they do not have a RhCE / RhD duplication.

In rare cases, the rhesus factor occurs only in a quantitatively weakened form (D u or D weak ). For the blood transfusion, such patients take a middle position between Rh-positive and Rh-negative. If they are to receive blood, they are transfused with Rh-negative blood. In contrast, patients with a qualitatively altered D antigen, so-called D partial , are Rh-negative.

Blood group compatibility

In the case of blood transfusion, blood groups are usually transfused from the same blood group, also with regard to the characteristics of the Rh system. However, there is a shortage of Rhd-negative blood donations .

  • The administration of Rhd-negative blood to RhD-positive patients poses no health problems; However, due to the availability situation, this does not usually occur.
  • The administration of RhD-positive blood to Rhd-negative patients is avoided whenever possible, but can often not be avoided due to the lack of Rhd-negative blood donations. Because of its importance in pregnancy, RhD-negative girls and women of childbearing potential are only given RhD-positive blood in life-threatening situations. After a transfusion of RhD-positive blood to Rhd-negative patients, a serological follow-up examination is carried out and, if antibodies are detected, the patient is advised about the risks and this complication is noted in the emergency passport .

If the RhD test is unclear, the patient's blood group is therefore usually shown as Rhd-negative.

receiver   Compatible EK (erythrocyte concentrates)
D negative D-negative,
D-positive only in life-threatening situations
D-positive D-positive,
possibly also D-negative (avoid if possible, as D-negative ECs are rare)

Conversion from rhesus negative to rhesus positive

According to some media reports, a 15-year-old girl in Sydney 2014 was the first to document a case of conversion of an originally Rhesus-negative patient to Rhesus-positive as a result of an organ transplant without the donor's blood cells or bone marrow cells being specifically transferred. The girl had received a donor liver from a rhesus-positive donor five years earlier. A blood group change, both of AB0 antigens and Rhesus features, ultimately with all detectable erythrocyte antigens, as a result of medical intervention is regularly observed in blood stem cell transplants of different blood groups . When selecting blood stem cell donors, the identity of the HLA antigens is the primary criterion, the blood group is a secondary criterion.

See also

Web links

Individual evidence

  1. a b Entry on Rhesus factors. In: Römpp Online . Georg Thieme Verlag, accessed on July 25, 2011. .
  2. Rhesus factor . In: Lexikon der Biologie , Wissenschaft Online; Retrieved March 17, 2010
  3. S. Biver et al .: A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility . In: Nature , 456, 2008, pp. 339-343
  4. G. Crombach, G. Giers: Clinical significance of the prenatal analysis of the fetal RhD genotype in the case of Rhesus incompatibility. In: MW Beckmann, P. Dall, Peter Fasching, J.-S. Krüssel, D. Niederacher, B. Tutschek (Editor): Molecular Medicine in Gynecology: Diagnostics and Therapy , p. 112.
  5. Haldane JBF: Selection against heterozygosis in Man. . In: Eugenics . 11, 1942, pp. 333-340. doi : 10.1111 / j.1469-1809.1941.tb02297.x .
  6. ^ RA Fisher, RR Race, GL. Taylor: Mutation and the Rhesus reaction . In: Nature . 153, 1944, p. 106. doi : 10.1038 / 153106b0 .
  7. CC Li: Is the Rh facing a crossroad? A critique of the compensation effect. . In: Am Naturalist. . 87, 1953, pp. 257-261. doi : 10.1086 / 281782 .
  8. M Novotná, J Havlícek, AP Smith, P Kolbeková, A Skallová, J Klose, Z Gasová, M Písacka, M Sechovská, J Flegr: Toxoplasma and reaction time: Role of toxoplasmosis in the origin, preservation and geographical distribution of Rh blood group polymorphism . In: Parasitology . 135, No. 11, 2008, pp. 1253-61. doi : 10.1017 / S003118200800485X . PMID 18752708 .
  9. J Flegr, M Novotna, J Lindová, J Havlícek: Neurophysiological effect of the Rh factor. Protective role of the RhD molecule against Toxoplasma -induced impairment of reaction times in women . In: Neuroendocrinology Letters . 29, No. 4, 2008, pp. 475-481. PMID 18766148 .
  10. J Flegr, J Klose, M Novotná, M Berenreitterová, J Havlícek: Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study . In: BMC Infect. Dis. . 9, 2009, p. 72. doi : 10.1186 / 1471-2334-9-72 . PMID 19470165 . PMC 2692860 (free full text).
  11. Willy A. Flegel: Genetics of the Rhesus blood group system. The Genetics of the Rhesus Blood Group System . In: Dtsch Arztebl , 2007, 104 (10), pp. A-651 / B-573 / C-549
  12. ^ RR Race, AE Mourant: The Rh Chromosome Frequencies in England . (PDF) In: American Society of Hematology (Ed.): Blood . 3, No. 6, USA, 1948, pp. 689-695. PMID 18860341 . Retrieved November 14, 2010.
  13. Hemotherapy. ( Memento of December 7, 2012 in the Internet Archive ) (PDF; 361 kB) Guidelines for the collection of blood and blood components and for the use of blood products. Section 4.3.5 Transfusion of red cell concentrates , German Medical Association, Paul Ehrlich Institute, changes and additions 2010, published in the Federal Gazette 2010; 62 (101a): 4-36.
  14. Erwin Strobel, Wolfgang Schramm: Blood group compatible selection of blood products. (PDF; 119 kB) In: Haemotherapy Forum, Bayrisches Ärzteblatt. 10/2003.
  15. Blood group changes after liver transplant. In: Die Welt , January 24, 2008, accessed May 26, 2013.
  16. Kate Sikora:Demi-Lee Brennan has changed blood types and immune system.In: The Daily Telegraph , January 25, 2008.
  17. Kaimo Hirv: HLA characteristics and bone marrow transplantation . Center for Human Genetics and Laboratory Diagnostics (MVZ), accessed on June 30, 2014.