The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation

Abstract

EBV reactivation is a serious complication affecting the recipients of allogeneic haematopoietic stem cell transplants (allogeneic HSCT). Recent reports have suggested that EBV reactivation induces increased expression of C-C chemokine receptor-5 (CCR5) or its ligands. Therefore, the 32-nucleotide deletion within the CCR5-encoding gene (CCR5D32 polymorphism) was analysed in 92 recipients of allogeneic HSCT and their donors and related with EBV load. In addition in 30 patients, at the same time points employing a real-time PCR technique, the number of viral copies and CCR5 transcripts were assessed. The incidence of EBV reactivation 2-3 months after transplantation was significantly lower in patients carrying the CCR5D32 allele (P ¼ 0.008). The association was confirmed in multivariate analysis, in which recipient CCR5D32 (OR ¼ 0.166, P ¼ 0.026) in addition to recipient age (OR ¼ 1.536, P ¼ 0.034) were identified as independent risk factors for EBV reactivation. Moreover, EBV reactivation was more frequently seen when patients and their donors were lacking the CCR5 deletion mutation as compared to other donor-recipient pairs (P ¼ 0.022). The CCR5 expression was significantly higher in the group of patients having EBV reactivation than in those lacking it (R ¼ 25.354, P ¼ 0.024). These results suggest that the expression of functional CCR5 plays a role in initiation/perpetuation of EBV reactivation.

Autocrine CCL3 and CCL4 Induced by the Oncoprotein LMP1 Promote Epstein-Barr Virus-Triggered B Cell Proliferation

“…Thus, CCL3 and CCL4 serve as survival and growth factors in B cells. In addition, patients carrying high copy numbers of EBV have significantly higher levels of CCR5, a binding receptor of CCL3 and CCL4 (24). In our study, we found that CCR5 is highly expressed during primary infection and constitutive expression is maintained in EBV-immortalized LCLs (data not shown).…”

“…In our study, we found that CCR5 is highly expressed during primary infection and constitutive expression is maintained in EBV-immortalized LCLs (data not shown). On the other hand, patients with a CCR5 gene deletion have a nonfunctional CCR5 chemokine receptor, leading to a low EBV load in sera after transplantation (24).…”

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

“…10,11 Supporting the role of CCR5 in GVHD, a single nucleotide polymorphism (SNP) in chemokine ligand 5 (CCL5, also known as RANTES) has been significantly associated with a greater incidence of chronic graft-versus-host disease (cGVHD). 12 The authors of another study 13 demonstrated that recipients with the nonfunctional CCR5⌬32 allele were less likely to develop acute graft-versushost disease (aGVHD), and other authors [14][15][16] have found CCR5 promoter polymorphisms to be predictive of the response to chemotherapy in leukemia and in the likelihood of cytomegalovirus and Epstein-Barr virus reactivation after HSCT.…”

“…[9][10][11][12][13][14][15][16] In particular, blockade or lack of the chemokine receptors CCR2 and CCR5 on donor leukocytes by administration of anti-CCR5 antibody or infusion of CCR2 Ϫ/Ϫ T cells reduces the incidence of GVHD in animal models. 10,11 Supporting the role of CCR5 in GVHD, a single nucleotide polymorphism (SNP) in chemokine ligand 5 (CCL5, also known as RANTES) has been significantly associated with a greater incidence of chronic graft-versus-host disease (cGVHD).…”

Beneficial effect of the CXCL12-3′A variant for patients undergoing hematopoietic stem cell transplantation from unrelated donors

“…Cytomegalovirus (CMV), Human Herpes Virus-6 (HHV-6), and Epstein-Barr Virus (EBV) reactivations were monitored in patients after transplantation using quantitative PCR as previously described [7][8][9][10]. In brief, DNA was extracted from peripheral blood (QiAmp Blood Kit; Qiagen, Hilden, Germany) according to the manufacturer's instructions.…”