Nondeletional ABO*O alleles express weak blood group A phenotypes

Owing to a single-base deletion, the vast majority of ABO*O alleles encode for a truncated and catalytically inactive ABO glycosyltransferase, leading to the generation of a premature stop codon. Less frequent nondeletional ABO*O alleles such as ABO*O03, in contrast, have nonsynonymous mutations that may abolish the protein's enzyme activity by altering its sugar-binding site.

Extensive ABO phenotyping and genotyping were performed in healthy blood group O donors with weak anti-A isoagglutinins and their relatives as well as in blood group O donors selected for the presence of ABO*O03. HeLa cells were used to transfect ABO expression plasmids.

Donors or relatives carrying ABO*O03 and/or its rare variant ABO*Aw08 in homozygous (n = 2) or heterozygous (n = 14) form showed weak A antigen expression detectable only by adsorption-elution (n = 15) or by monoclonal anti-A typing (n = 1). The serum samples of most donors (n = 13) contained weak anti-A; in the remaining donors, anti-A isoagglutinin reactivity was in the normal range. In the transfection studies, weak A antigen expression on HeLa cells transfected with plasmids containing ABO*O03 or ABO*Aw08 expression constructs was detectable only by adsorption-elution.

The data provide evidence that nondeletional ABO*O03-like alleles produce detectable amounts of A antigens.