Association Of Il-10 And Il-10 Receptor Gene Polymorphisms And Graft-Versus-Host Disease Following Hematopoietic Cell Transplantation.

Abstract Polymorphisms in cytokine genes can influence immune responses and may affect the outcome of hematopoietic cell transplantation (HCT). We have shown that the IL-10/-592*A allele of the recipient is a marker for less severe acute graft-versus-host disease (GVHD) and a lower risk of non-relapse mortality (NRM) after HCT from an HLA-identical sibling (N Engl J Med, 2003). To further test the hypothesis that IL-10 pathway is important in the intensity of acute GVHD, we undertook a study of variation in the IL-10 receptor β gene. A single nucleotide polymorphism (A/G) at cDNA position 238 of the IL-10 receptor β gene (IL-10RB/1304) was genotyped in 953 HCT recipients and their HLA-identical sibling donors. IL-10/-592 and IL-10RB alleles and genotypes were tested for association with GVHD by multivariable analysis. The IL-10/-592*A allele of the recipient and IL-10RB/238*G allele of the donor were significantly associated with a lower risk of acute grades III-IV GVHD (trend p value 0.0008 and 0.02, respectively). None of the 16 cases with a patient IL-10 A/A genotype and donor IL-10RB G/G genotype developed grades III-IV acute GVHD (HR = 0.0 and p value = 0.007), compared to pairs with a patient IL-10 C/C genotype and donor IL-10RB A/A genotype. The hazard ratios were 0.4–0.6 among pairs with a patient IL-10 A/A genotype and donor IL-10RB A/G or A/A genotype and among pairs with a patient IL-10 A/C genotype and donor IL-10RB G/G or A/G genotype. The effect of donor IL-10RB genotype on GVHD was observed only among pairs with a patient IL-10 A/C or A/A genotype (trend p value = 0.005 and 0.06 respectively), but not among pairs with a patient IL-10 C/C genotype (trend p value = 0.82). These data suggest an interaction in the effect of the patient IL-10/-592 and donor IL-10RB/1304 genotypes on GVHD, further supporting the hypothesis that the IL-10 pathway plays an important role in controlling the severity of acute GVHD.