CCR5 and RANTES/CCL5 Gene Polymorphisms Affect the Risk of EBV Reactivations after Allogeneic HSCT.

Abstract

Epstein-Barr virus (EBV) reactivation is a serious complication affecting the recipients of allogeneic hematopoietic stem cell transplants (HSCT). Chemokines and their receptors play a major role in the inflammatory and immune responses that mediate allograft outcome. CC-chemokine receptor-5 (CCR5) is known to be involved in perpetuation of HIV infection (as a co-receptor for HIV entry) and the clinical course of this infection is favored by the presence of the 32-nucleotide deletion within the CCR5 gene (CCR5Δ32 polymorphism). The CCR5 deletion mutation (CCR5Δ32) results in a non-functional chemokine receptor. In the present study the CCR5Δ32 polymorphism and two single nucleotide substitutions (−28 C/G; −403 G/A) within, one of the CCR5 ligands, the CCL5/RANTES gene were analyzed in 75 HSCT recipients, 75 donors and related with EBV load. The control group constituted 99 healthy individuals. DNA was extracted from peripheral blood taken into EDTA using silica membranes. Viral load were assessed 2-3 moths after transplantation in blood cells employing a real-time PCR technique. The detection threshold for viral reactivation equaled 10 EBV-DNA copies/105 peripheral blood cells. EBV reactivation was detected in 26 patients. The CCR5Δ32 and RANTES (−28 C/G; −403 G/A) polymorphisms were analyzed by PCR and PCR-RFLP technique, respectively. Distributions of CCR5 and RANTES −28 genotypes were similar in patients, donors and healthy individuals. RANTES −403 AA homozygosity was more frequent in donors than controls (0.61 vs 0.47, p=0.036). The higher number of EBV copies was detected in patients lacking CCR5Δ32 deletion (0.92 vs 0.71, p=0.031). No significant correlation between EBV reactivation and RANTES −28 C/G polymorphism. However, patients transplanted with donors homozygous for RANTES −403 AA (genotype associated with an increased expression of the RANTES gene) more frequently presented with EBV reactivation (0.85 vs 0.49, p=0.002). In conclusion, the presence of the CCR5 deletion-mutation in the recipient and RANTES-403 G in the donor of HSC appeared to lower the susceptibility for EBV reactivation.