Genetic variation in the IL-10 pathway modulates severity of acute graft-versus-host disease following hematopoietic cell transplantation: synergism between IL-10 genotype of patient and IL-10 receptor beta genotype of donor.
We have previously shown that the interleukin 10 (IL-10)/-592*A allele of the recipient is associated with less severe acute graft-versus-host disease (GVHD) and a lower risk of nonrelapse mortality after hematopoietic cell transplantation (HCT) from an HLA-identical sibling. In the present study, we examined variation in the IL-10 receptor beta gene as a further test of the hypothesis that the IL-10 pathway regulates the risk of acute GVHD. A single nucleotide polymorphism (A/G) at cDNA position 238 of the IL-10 receptor beta gene (IL10RB/c238) was genotyped in 953 HC transplant recipients and their HLA-identical sibling donors. IL-10/-592 and IL10RB/c238 genotypes were tested for association with GVHD by multivariable analysis. The IL-10/-592*A allele of the recipient and IL10RB/c238*G allele of the donor were significantly associated with a lower risk of grades III-IV acute GVHD (trend P < .001 and P = .02, respectively). The donor IL10RB/c238*G allele provided protection among patients with the IL-10/-592 A/C or A/A genotypes but not among patients with the high-risk IL-10/-592 C/C genotype. These data suggest an interaction of the patient IL-10/-592 and donor IL10RB/c238 genotypes on risk of GVHD, further supporting the hypothesis that the IL-10 pathway plays an important role in controlling the severity of acute GVHD.
Lin
Ming-Tseh
MT
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D2-100, PO Box 19024, Seattle, WA 98109-1024, USA.
Storer
Barry
B
Martin
Paul J
PJ
Tseng
Li-Hui
LH
Grogan
Bryan
B
Chen
Pei-Jer
PJ
Zhao
Lue P
LP
Hansen
John A
JA
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006086:Graft vs Host Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006648:Histocompatibility / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D053701:Receptors, Interleukin-10; D012307:Risk Factors; D014019:Tissue Donors
D006680:HLA Antigens; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10