Rhesus blood group

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See also Blood groups

An erythrocyte membrane protein complex with a role in maintaining erythrocyte membrane integrity[1] and possible roles as an ammonium transporter.[2]

Polymorphisms in the gene determine the Rhesus blood group status. It is clinically relevant in transfusion and also in pregnancy as Rhesus negative mothers carrying Rhesus positive babies can become sensitised to the antigen. The anti-Rhesus antibodies, commonly against the D antigen (see below), often do not develop till late in the pregnancy so that the index pregnancy is unaffected. However, subsequent Rhesus positive babies are at serious risk of intra-uterine haemolysis, causing erythroblastosis fetalis, or at term, it is one of several causes of haemolytic disease of the newborn.

2 of the subunits of the protein complex are thought to be coded by two gene loci, Rhesus D (RHD) and Rhesus C/E (RHCE). Both gene loci are highly homologous (92%) and tightly linked on chromosome 1.

Several possible genotypes are possible from the various permutations and combinations of c/C, d/D and e/E. The cde genotype is classed as Rhesus antigen negative. Rhesus negativity is more common in Europeans (allele frequency 40-45%, equivalent to 15% of population). The allele is less common in Africans (allele frequency 3%, 0.1% prevalence) and even less common in Asians (allele frequency about 1%, 0.01% prevalence).

Further variation in the Rhesus complex is possible due to polymorphisms in the remaining non-CDE subunits (RHAG).[3] Several rare variants of RHD are recognised. These mutations may render the protein sufficiently different that it is not detected by standard methods of testing, i.e. despite having RHD protein, normal blood grouping will give a false negative. These individuals have a risk of alloimmunisation when transfused.


So named as the discovery of the Rhesus factor was from experiments on the M- and N- groups in blood from Rhesus monkeys (which share the antigen with humans). First identified in 1937, but the original paper was not published until 1940[4]

Alloimmunisation in Pregnancy

Immunoprophylaxis consists of giving the mother Rhesus D immunoglobulin prior to the mother becoming alloimmunised to the antigen. This is a form of passive immunisation and it prevents future problems by 'mopping' up RhD antigen on fetal red cells in the maternal circulation before cellular immunity is triggered to develop memory.

It should be given:[5][6][7]

Studies analysing fetal DNA within the maternal circulation have been able to determine the fetal blood group in 95.7% of cases and may allow selective administration of anti-D antibodies to only those that are at risk.[8]