Rh System
The Rh system is the most complex one, having over 50 antigens beyond RhD. However, only some of them are commonly encountered. The Rh system is encoded by two homologous genes located on chromosome 1. RHD encodes the D antigen, and RHCE encodes the C, c, E and e antigens. The opposing orientation of the RHD and RHCE genes on the same chromosome facilitates a hairpin loop formation, leading to genetic recombination, which in turn results in multiple RhD and/or RhCE variants.
RHD and RHCE variants are not uncommon in patients of African ethnicity, which is one reason why the selection of RBCs for patients with sickle cell disease can occasionally be challenging.
RH notation
Despite the multitude of RHD and RHCE variants, the most common alleles are the D, C, c, E and e antigens that give these two genes their names. Antigens with capital letters are generally less frequent than those with lower case letters, reflecting the relative frequency with which the corresponding antibodies are encountered. For example, anti-C is encountered more often than anti-c, because there are more people who express the c antigen.
Several notations exist to describe the different possible haplotypes that are possible with the D, C, c, E and e antigens. Below is a table of the commonly used Fisher-Race and Weiner nomenclatures. The capital “R” in the Weiner notation denotes the expression of RhD antigen, while “r” represents its absence. Amongst RhD positive patients (“R”), the subscript 0 indicates the presence of the ce antigens in cis, 1 represents Ce, 2 represents cE, and Z represents CE. Amongst RhD-negative patients (“r”), the absence of any subscript indicates the ce antigens in cis, a single apostrophe indicates Ce, a double apostrophe indicates cE, and the letter y indicates CE. This notation is summarized in the table below:
As each haplotype in the above table is inherited from a single parent, two instances are required to denote the entire Rh phenotype of an individual. For example, R1R1 indicates that the patient expresses just the D, C and e antigens, each with a double “dose” (ie., high antigen expression) due to homozygosity. R1r indicates expression of the D, C, c, and e antigens. In this case, D, C, and c are expressed with a single “dose”; e is expressed with a double “dose”.
Of note, the frequency of the different haplotypes varies depending on ethnic origin. For example, amongst Caucasians the most common RhD-positive haplotypes are R1 and R2, while amongst those of African ethnicity the most common RhD-positive haplotype is R0. This is one reason why transfusing sickle cell patients are at high risk of making anti-C and anti-E antibodies. Amongst both type, the most common RhD-negative haplotype is r.
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