RANTES Polymorphisms and the Risk of Graft-versus-Host Disease in Human Leukocyte Antigen-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

We investigated the association between RANTES (regulated upon activation, normal T cell expressed and secreted) polymorphisms and clinical outcomes in patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Three RANTES gene polymorphisms, i.e. –403G/A (rs2107538), –28C/G (rs2280788) and In1.1T/C (rs2280789), were genotyped, and the effects of the genotypes and haplotypes of RANTES on clinical outcomes were analyzed. The competing risk regression analysis was used to investigate the relationship between the polymorphisms and the cumulative risk of graft-versus-host disease (GVHD). An AGC haplotype in a recessive model showed significant harmful effects on the cumulative risk of acute GVHD and relapse-free survival (adjusted hazard ratios 2.42 and 2.71, 95% confidence intervals 1.29–4.55 and 1.30–5.64; p = 0.018 and 0.024, respectively), whereas a GCT haplotype did not. RANTES polymorphisms were not significantly associated with overall survival and the risk of chronic GVHD. This study suggests that RANTES polymorphisms might be associated with the occurrence of acute GVHD rather than of chronic GVHD and also of relapse-free survival in the patients treated with allo-HSCT. Further larger prospective investigations are needed to establish the role of RANTES polymorphisms in patients treated with allo-HSCT.

From genetic single candidate gene studies to complex genomics of GvHD

“…Similar relationships were observed for recipients with AG haplotype [CCL5-403 (rs2107538)/CCL5-28 (rs1800825)]. On the other hand, Shin et al (2013), who analysed three CCL5 polymorphisms, -403G/A (rs2107538), -28C/G (rs2280788) and In1.1T/C (rs2280789), showed significant effects of the AGC haplotype on the cumulative risk of aGvHD and relapse-free survival.…”

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

“…Also in mice, anti-CD3 treatment during preconditioning reduced aGvHD by limiting both CCR7 + dendritic cells homing to lymph nodes and CCR9 + effector T cells homing to aGvHD target organs without reducing GvL [179]. In humans, both a CCL5 (RANTES; Regulated on Activation, Normal T Cell Expressed and Secreted) haplotype of three polymorphisms [180] and the expression of the CX3CL1/CX3CR1 pair [181] positively correlated with the occurrence of aGvHD. Depending on the cells bearing GPCRs, other chemokine receptors can prevent aGvHD.…”

The Relationship of CCL5 and CCR1 Variants with Response Rate and Survival Taking into Account Thalidomide/Bortezomib Treatment in Patients with Multiple Myeloma

“…Kim and colleagues showed that the CG genotype of rs2280788 in recipients of allo-HSCT was significantly associated with a higher incidence of chronic GVHD, extensive chronic GVHD, and severe grade of chronic GVHD compared to CC genotype [ 48 ]. In contrast, a study by Shin et al suggested that CCL5 variants may be associated with acute GVHD rather than chronic GVHD, as well as relapse-free survival in patients treated with allo-HSCT [ 49 ]. In the studies presented above, CCL5 polymorphisms have been rather negative prognostic factors of the risk of developing graft versus host disease.…”