Contribution of TNF-alpha and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation

Some cytokines are believed to play a role in the development of acute and chronic GVHD after allo-hematopoietic stem cell transplantation. It has bee n reported that TNF-alpha and IL-10 gene polymorphisms are associated with the production of those cytokines and the development of graft failure afte r organ transplantation and systemic lupus erythematosus. We examined wheth er TNF-alpha and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis of aGVHD and cGVHD, respectively. We analyzed the gene po lymorphisms derived from pre- and post-transplant blood cells, Donor-derive d TNF2 allele (A) was more frequently detected in patients with aGVHD III/I V than those aGVHD 0-11 (2/6 vs 2/56) (P = 0.04). The donors of the patient s with cGVHD more frequently possessed a greater number of alleles (allele 13 or more which contain 26 or more CA repeats) in IL-10(.)G than those wit hout (13/26 vs 5/28) (P = 0,02), and the patients with cGVHD had more CA re peats in donor-derived IL-10(.)G than those without (mean = 25.2 vs 23.4) ( P = 0.01). Donor-derived TNF-308 and IL-10(.)G alleles may contribute to se vere aGVHD and cGVHD, respectively, and will help us distinguish those pati ents at high risk for GVHD.