A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

Abstract

IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLAmatched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P ¼ 0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI,; P ¼ 0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P ¼ 0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.

Il-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-Versus-Host Disease

“…Previous studies showed association between G197A polymorphism and several chronic diseases [12], like ulcerative colitis [19] and rheumatoid arthritis [20]. A study reported association between allele A of IL17A polymorphism and high risk of cGVHD [12]. Until now, no other work was reported in the literature relating IL17F polymorphism and GVHD.…”

“…Several studies have been devoted to analyze the role of IL-17, a new discovered cytokine, in the pathogenesis of GVHD [12,[16][17][18]. However, this is the first work that evaluated both cytokines IL-17A and IL17F, involving the genetic and phenotypic aspects, and investigated the immunophenotypic aspect of IL-17A regarding systemic cGVHD.…”

“…In the current study we investigate the involvement of the IL17A and IL17F gene polymorphism in the cGVHD and our results showed association of AA recipient genotypes with the occurrence of systemic cGVHD. Previous studies showed association between G197A polymorphism and several chronic diseases [12], like ulcerative colitis [19] and rheumatoid arthritis [20]. A study reported association between allele A of IL17A polymorphism and high risk of cGVHD [12].…”

“…In few recent studies, IL-17A has been associated with the pathway of the GVHD and some studies have assessed the association between IL17A gene polymorphism and inflammatory diseases, including the cGVHD [6,11,12]. However, the role of IL-17F in the pathogenesis of cGVHD was not previously addressed.…”

IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

“…Several studies have been devoted to analyze the role of IL-17, a new discovered cytokine, in the pathogenesis of GVHD [12, 16–18]. However, this is the first work that evaluated both cytokines IL-17A and IL17F, involving the genetic and phenotypic aspects, and investigated the immunophenotypic aspect of IL-17A regarding systemic cGVHD.…”