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 sialoglycoproteins, GPA and GPB, encoded by GYPA and GYPB . The molecular backgrounds of the low-frequency antigens Ny a 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 single-strand conformation polymorphism analysis, and exon 3 was sequenced. Synthetic 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-Os a and an MAIEA assay with MoAbs to GPA showed that Os a is on GPA. Sequencing exon 3 of an Os(a+) person from the only family with Os a revealed heterozygosity for a C273T base change encoding a Pro54Ser substitution. A synthetic peptide representing part of GPA with the Os a mutation (VRTVYP S EEETGE) completely inhibited anti-Os a , whereas the control peptide (VRTVYP P EEETGE) did not inhibit anti-Os a . CONCLUSION: Ny a and Os a are low-frequency antigens of the MNS blood group system that represent Asp27Glu and Pro54Ser substitutions in GPA, respectively.