HLA-A amino acid polymorphism and delayed kidney allograft function.
Delayed allograft function (DGF) is a common adverse event in postrenal transplantation. The etiology of DGF is thought to include both nonimmunologic (donor age, cold ischemia time, and recipient race) and immunologic factors. We examined the association of DGF with amino acid mismatches at 66 variable sites of the HLA-A molecule in a prospective cohort study of 697 renal transplant recipients of deceased donors. Using a multivariate logistic regression model adjusted for nonimmunologic risk factors, we show that combinations of a few amino acid mismatches at crucial sites of HLA-A molecules were associated with DGF. In Caucasian recipients, a mismatch at position 62, 95, or 163, all known to be functionally important within the antigen recognition site, was associated with an increased risk for DGF. Furthermore, a decreased risk for DGF was associated with a mismatch at HLA-A family-specific sites (149, 184, 193, or 246), indicating that evolutionary features of HLA-A polymorphism separating HLA-A families and lineages among donor-recipient pairs may correlate with the magnitude of alloreactivity influencing the development of DGF. These findings suggest that amino acid polymorphisms at functionally important positions at the antigen recognition site of the HLA-A molecule have a significant influence on DGF.
Kamoun
Malek
M
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. malekkam@mail.med.upenn.edu
Holmes
John H
JH
Israni
Ajay K
AK
Kearns
Jane D
JD
Teal
Valerie
V
Yang
Wei Peter
WP
Rosas
Sylvia E
SE
Joffe
Marshall M
MM
Li
Hongzhe
H
Feldman
Harold I
HI
D000596:Amino Acids / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006648:Histocompatibility / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014184:Transplantation, Homologous / Q000276:immunology
D000596:Amino Acids; D006680:HLA Antigens