TY - JOUR
T1 - Mapping MHC-Resident Transplantation Determinants
AU - Malkki, M.
AU - Gooley, T.A.
AU - Horowitz, M.M.
AU - Absi, L.
AU - Christiansen, Frank
AU - Cornelissen, J.J.
AU - Dormoy, A.
AU - Dubois, V.
AU - Gagne, K.
AU - Gluckman, E.
AU - Haagenson, M.D.
AU - Oudshoorn, M.
AU - Spellman, S.
AU - Petersdorf, E.W.
PY - 2007
Y1 - 2007
N2 - Graft-versus-host disease (GVHD) accounts for increased morbidity and mortality after HLA-identical unrelated hematopoietic cell transplantation (HCT). To test the hypothesis that the major histocompatibility complex (MHC) encodes functional variation other than the classical HLA genes, we measured risks associated with donor-recipient MHC microsatellite (Msat) marker mismatching in 819 HCT recipients and their HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors. Suggestive trends of association with transplant outcome were observed for 5 Msats. Donor-recipient mismatching for the extended class I D6S105, class III D6S2787, and class II D6S2749 markers was each associated with an increased risk of death (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P =.03; hazard ratio, 1.26; 95% confidence interval, 1.03-1.53; P =.02; hazard ratio, 1.37; 95% confidence interval, 1.08-1.72; P =.007, respectively) whereas mismatching for the class I D6S2811 marker was associated with a decreased risk of death (hazard ratio, 0.80; 95% confidence interval, 0.66-0.98; P =.03). Mismatching for the class I D6S265 marker was associated with a decreased risk of grades III-IV acute GVHD (odds ratio, 0.67; 95% confidence interval, 0.45-0.98; P =.04). These results suggest that Msats may be informative for mapping MHC-resident genetic variation of clinical importance in HCT. (c) 2007 American Society for Blood and Marrow Transplantation.
AB - Graft-versus-host disease (GVHD) accounts for increased morbidity and mortality after HLA-identical unrelated hematopoietic cell transplantation (HCT). To test the hypothesis that the major histocompatibility complex (MHC) encodes functional variation other than the classical HLA genes, we measured risks associated with donor-recipient MHC microsatellite (Msat) marker mismatching in 819 HCT recipients and their HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors. Suggestive trends of association with transplant outcome were observed for 5 Msats. Donor-recipient mismatching for the extended class I D6S105, class III D6S2787, and class II D6S2749 markers was each associated with an increased risk of death (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P =.03; hazard ratio, 1.26; 95% confidence interval, 1.03-1.53; P =.02; hazard ratio, 1.37; 95% confidence interval, 1.08-1.72; P =.007, respectively) whereas mismatching for the class I D6S2811 marker was associated with a decreased risk of death (hazard ratio, 0.80; 95% confidence interval, 0.66-0.98; P =.03). Mismatching for the class I D6S265 marker was associated with a decreased risk of grades III-IV acute GVHD (odds ratio, 0.67; 95% confidence interval, 0.45-0.98; P =.04). These results suggest that Msats may be informative for mapping MHC-resident genetic variation of clinical importance in HCT. (c) 2007 American Society for Blood and Marrow Transplantation.
U2 - 10.1016/j.bbmt.2007.05.007
DO - 10.1016/j.bbmt.2007.05.007
M3 - Article
C2 - 17640603
SN - 1083-8791
VL - 13
SP - 986
EP - 995
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -