The low-frequency MNS blood group antigens Ny(a) (MNS18) and Os-a (MNS38) are associated with GPA amino acid substitutions

BACKGROUND: Antigens of the MNS blood group system are located on two sialo glycoproteins, GPA and GPB, encoded by GYPA and GYPB. The molecular backgro unds of the low-frequency antigens Nye and Os-a are not known. STUDY DESIGN AND METHODS: Immunoblotting and a monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay were used to analyze Os-a. PCR-amplified products of the coding exons of GYPA were studied by si ngle-strand conformation polymorphism analysis, and exon 3 was sequenced. S ynthetic peptides were used in hemagglutination-inhibition tests. RESULTS: Sequencing of GYPA exon 3 of two unrelated Ny(a+) persons revealed heterozygosity for a T194A base change encoding an Asp27Glu substitution. Immunoblotting with anti-Osp and an MAIEA assay with MoAbs to GPA showed th at Os-a is on GPA. Sequencing exon 3 of an Os(a+) person from the only fami ly with Os-a revealed heterozygosity for a C273T base change encoding a Pro 54Ser substitution. A synthetic peptide representing part of GPA with the O s-a mutation (VRTVYPSEEETGE) completely inhibited anti-Os-a, whereas the co ntrol peptide (VRTVYPPEEETRGE) did not inhibit anti-Os-a. CONCLUSION: Ny(a) and Os-a are low-frequency antigens of the MNS blood grou p system that represent Asp27Glu and Pro54Ser substitutions in GPA, respect ively.