An age-dependent ABO discrepancy between mother and baby reveals a novel A(weak) allele.

ABSTRACT

BACKGROUND: Discrepancies in ABO grouping arise due to different reasons, posing a threat to patient safety. Underlying causes include mixed-field agglutination after transfusion, chimerism, fetomaternal exchange, or inheritance of unusual alleles resulting in weak A/B antigen expression. Cord blood from the infant of a group A2 B mother typed as group O, H+. Samples were investigated to elucidate this conundrum. STUDY DESIGN AND METHODS: Genomic DNA was analyzed by ABO genotyping and sequencing. Red blood cells (RBCs) were characterized by routine serology and flow cytometry. Glycosyltransferase structure was predicted with 3D-modeling software. RESULTS: The mother genotyped as ABO*A1.01/B.01, and the baby, ABO*A1.01/O.01.01. Sequencing revealed a substitution, 311T>A, in the ABO*A1-like allele, which predicts Ile104Asn. Flow cytometry demonstrated A antigen on the mother's RBCs equivalent to the A2 phenotype while no A was detectable on cord RBCs. However, blood from the 11-month-old child demonstrated markedly increased A expression, likely reflecting initiation of carbohydrate chain branching. CONCLUSION: We unraveled a novel A(weak) allele (ABO*AW.29) in a case of apparent nonmaternity. Residue 104 is far from the catalytic site and may be involved in stabilizing the glycosyltransferase by dimerization. Our data support that the group AB mother's B-transferase stabilizes the altered A-transferase by heterodimerization, exemplifying the allelic enhancement phenomenon.