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.
Transpl Int
; 23(12): 1216-22, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20536911
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article