IL-10 promoter polymorphisms influence susceptibility to aGvHD and are associated with proportions of CD4+FoxP3+ lymphocytes in blood after hematopoietic stem cell transplantation

摘要

Four hundred and ninety-five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin-10 (IL-10) promoter genotype [rs18000896 (-1082 G/A), rs18000871 (-819 C/T) and rs18000872 (-592 C/A)] on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, gradeI) if transplanted from human leukocyte antigen (HLA) well-matched (10/10) unrelated donors (20/135 vs 39/117, P0.001, Pcorr=0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P=0.019, Pcorr=0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor-recipient human leukocyte antigen (HLA) mismatch [odds ratio (OR)=3.937, P=0.001] and a lack of ACC haplotype in recipients (OR=0.417, P=0.013) played a significant role as independent risk factors of aGvHD gradeI. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL-10 haplotypes. It was seen at the time of hematological recovery (mean±SEM: 3.80±0.91% vs 2.06±0.98%, P=0.012) and 2weeks later (5.32±0.87% vs 2.50±0.83%, P=0.013); -592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P=0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43±0.22% vs 4.32±0.71%, P=0.051) measured 2weeks after hematological recovery. Functional IL-10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.