1. Molecular and structural characterization of a novel high-prevalence antigen of the Augustine blood group system.
- Author
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Vrignaud C, Mikdar M, Duval R, Reininger L, Damaraju VL, Sawyer M, Colin Y, Le Van Kim C, Gelly JC, Etchebest C, Peyrard T, and Azouzi S
- Subjects
- Pregnancy, Female, Humans, HEK293 Cells, Prevalence, Isoantibodies, Molecular Structure, Blood Group Antigens genetics
- Abstract
Background: An antibody directed against a high-prevalence red blood cell (RBC) antigen was detected in a 67-year-old female patient of North African ancestry with a history of a single pregnancy and blood transfusion. So far, the specificity of the proband's alloantibody remained unknown in our immunohematology reference laboratory., Study Design and Methods: Whole-exome sequencing (WES) was performed on the proband's DNA. The reactivity to the SLC29A1-encoded ENT1 adenosine transporter was investigated by flow cytometry analyses of ENT1-expressing HEK293 cells, and RBCs from Augustine-typed individuals. Erythrocyte protein expression level, nucleoside-binding capacity, and molecular structure of the proband's ENT1 variant were further explored by western blot, flow cytometry, and molecular dynamics calculations, respectively., Results: A missense variant was identified in the SLC29A1 gene, which encodes the Augustine blood group system. It arises from homozygosity for a rare c.242A > G missense mutation that results in a nonsynonymous p.Asn81Ser substitution within the large extracellular loop of ENT1. Flow cytometry analyses demonstrated that the proband's antibody was reactive against HEK-293 cells transfected with control but not proband's SLC29A1 cDNA. Consistent with this finding, proband's antibody was found to be reactive with At(a-) (AUG:-2), but not AUG:-1 (null phenotype) RBCs. Data from structural analysis further supported that the proband's p.Asn81Ser variation does not alter ENT1 binding of its specific inhibitor NBMPR., Conclusion: Our study provides evidence for a novel high-prevalence antigen, AUG4 (also called ATAM after the proband's name) in the Augustine blood group system, encoded by the rare SLC29A1 variant allele AUG*04 (c.242A > G, p.Asn81Ser)., (© 2023 AABB.)
- Published
- 2023
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