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Mapping MHC-resident transplantation determinants. Biol Blood Marrow Transplant 2007 Aug;13(8):986-95 PMID: 17640603 PMCID: PMC3182140

Pubmed ID

17640603

Abstract

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.

Author List

Malkki M, Gooley TA, Horowitz MM, Absi L, Christiansen FT, Cornelissen JJ, Dormoy A, Dubois V, Gagne K, Gluckman E, Haagenson MD, Oudshoorn M, Spellman S, Petersdorf EW, International Histocompatibility Working Group in Transplantation

Author

Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-34447302894   15 Citations

MESH terms used to index this publication - Major topics in bold

Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Linkage Disequilibrium
Major Histocompatibility Complex
Male
Microsatellite Repeats
Polymorphism, Genetic
Predictive Value of Tests
Retrospective Studies
Survival Analysis
Transplantation, Homologous
Treatment Outcome
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916