Of the 43 blood group systems identified, only a small number of antigens remain uncharacterized. Era is a high incidence red blood cell (RBC) antigen that was identified in 1982 with low-incidence antigens Erb and Er3 identified shortly thereafter. Data on the Er blood group antigens are scarce. To gain a better understanding of this group of RBC antigens, researchers in the United Kingdom performed Sanger or whole exome sequencing on individuals (N=13) with serologically defined Er alloantibodies and identified low frequency missense mutations in the PIEZO1 gene. Based on sequence data and the serological characterization of these 13 alloimmunized individuals and some of their relatives, researchers defined the genetic basis for the known Er antigens (Era, Erb, and Er3) and identified two other low-frequency Er antigens (Er4 and Er5). The researchers further confirmed that Piezo1 (a large, mechanosensitive nonselective cation channel in a variety of tissues) is the carrier molecular for the Er RBC antigens based on immunoprecipitation, CRISPER/Cas9-mediated gene knockout, and overexpression in an erythroblast cell line. Further research on this blood group system is warranted as anti-Er4 and anti-Er5 have both been implicated in hemolytic disease of the fetus and newborn. In addition, PIEZO1 is highly polymorphic, and it is likely that further Er RBC antigens will be identified.
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