Mapping MHC-resident transplantation determinants.
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.
Malkki
Mari
M
The Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Gooley
Ted A
TA
Horowitz
Mary M
MM
Absi
Lena
L
Christiansen
Frank T
FT
Cornelissen
Jan J
JJ
Dormoy
Anne
A
Dubois
Valerie
V
Gagne
Katia
K
Gluckman
Eliane
E
Haagenson
Michael D
MD
Oudshoorn
Machteld
M
Spellman
Stephen
S
Petersdorf
Effie W
EW
D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D018895:Microsatellite Repeats / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000276:immunology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000295:instrumentation; D016896:Treatment Outcome