Impact of amino acid substitution at residue 9 of HLA-A2 on the development of acute GVHD in Korean pediatric patients receiving unrelated hematopoietic stem cell transplantation

Abstract

Incompatibility of human leukocyte antigen (HLA) alleles between donors and recipients of unrelated hematopoietic stem cell transplantation (UHSCT) increases the risk of acute graft-versus-host disease (GVHD). We evaluated the positional effect of amino acid substitutions in HLA molecules on severe acute GVHD in Korean pediatric recipients of UHSCT. All of 64 donor-recipient pairs were serologically matched for HLA-A, -B, and -DR loci. Only substitution at residue 9 resulting from an HLA-A*02 polymorphism was significantly associated with the risk of severe acute GVHD in patients (OR=7.0, P=0.033) on multivariate analysis. Recipients of this mismatched HLA also showed shortened overall survival (HR=9.7, P<0.001) and increased risk for transplant-related mortality (HR=9.1, P=0.027). Structural modeling showed that the amino acid substitution could alter the peptide preference of the ligand-binding pocket. A single amino acid substitution at position 9 was a major predictor of severe acute GVHD in Korean pediatric patients.