Molecular and structural characterization of a novel high-prevalence antigen of the Augustine blood group system.
Transfusion
; 63(3): 610-618, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36744388
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 ANDMETHODS:
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).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Grupos Sanguíneos
Tipo de estudo:
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Transfusion
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França