Functional polymorphism of CTLA-4 and ICOS genes in allogeneic hematopoietic stem cell transplantation

Background: T cells play a critical role in alloimmune recognition and thus contribute to graft-versus-host disease (GVHD) and relapse prevention in hematopoietic stem cell transplantation (HSCT). Cytotoxic T lymphocyte antigen-4 (CTLA-4) and inducible costimulator (ICOS) are costimulatory molecules of T cell activation and their genetic variations can affect the capacity of T cells to become activated or inactivated. Methods: We examined CTLA-4 (-318 C/T and +49 A/G) and ICOS (c.602 A/C and c.1624 C/T) genotypes in 123 patients with HSCT and their HLA-matched sibling donors, and then evaluated the impacts of the genetic polymorphisms on GVHD, disease relapse, and survival. Results: By multivariate analysis, the donor CTLA-4 - 318 TT genotype increased the risk of disease relapse (Hazard ratio [HR]: 5.91, 95% confidence interval [CI]: 1.17-29.79, P=0.0313). Recipients who received a graft from a donor with ICOS c.602 CC genotype had worse disease-free survival (HR: 5.97, 95% CI: 1.49-23.87, P=0.0115). Additionally, recipients with ICOS c.1624 TT genotype had worse overall survival (HR: 12.98. 95% Cl: 2.58-65.35, P=0.0019). Nevertheless, CTLA-4 and ICOS genotypes were not associated with acute and chronic GVHD. Conclusions: Both donor and recipient CTLA-4 and ICOS gene polymorphisms might be of importance for the outcome of allogeneic HSCT. (C) 2009 Elsevier B.V. All rights reserved.