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.
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.
Hwang
Sang-Hyun
SH
Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea.
Oh
Heung-Bum
HB
Choi
Sung-Eun
SE
Seo
Jong-Jin
JJ
Lee
Jae-Hwan
JH
Cho
Sung-Woo
SW
Chae
Jeong-Min
JM
Heo
Yong-Seok
YS
Chang
Chulhun L
CL
Lee
Eun-Yup
EY
D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008958:Models, Molecular; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D056910:Republic of Korea
D015789:HLA-A2 Antigen