transplantation from HLA-identical sibling donors CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell

Abstract CTLA-4 is an inhibitory molecule that downregulates T-cell activation. Although polymorphisms at have been correlated with autoimmune diseases their CTLA-4association with clinical outcome after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has yet to be explored. Five CTLA-4 single-nucleotide polymorphisms were genotyped on 536 HLA-identical sibling donors of allo-HSCT. Genotypes were tested for an association with patients’ post-transplant outcome. The effect of the polymorphisms on CTLA-4 mRNA and protein production were determined in 60 healthy controls. We observed a reduction in the mRNA expression of the soluble CTLA-4 isoform in the presence of a G allele at CT60 and +49. Patients receiving stem cells from a donor with at least one G allele in position CT60 had worse overall survival (56.2% vs . 69.8% at 5 years; p: 0.001; HR: 3.80; 95% CI: 1.75-8.22), due to a higher risk of relapse (p: 0.049; HR: 1.71; 95% CI: 1.00-2.93). Acute graft-versus-host disease (aGVHD) was more frequent in patients receiving CT60 AA stem cells (P: 0.033; HR: 1.54; 95% CI: 1.03-2.29). This is the first study to report an association between polymorphisms at