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

Abstract

Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P ‫؍‬ .005) and overall survival (P ‫؍‬ .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P ‫؍‬ .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. (Blood.

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

“…2 Previous investigations have revealed that several single-nucleotide polymorphisms (SNPs), which impact on individual immune response to infections and inflammatory reactions are associated with SCT outcomes including the risk of acute GVHD. [3][4][5][6][7][8][9][10][11][12] IL-17, also known as IL-17A, is the hallmark cytokine of a new T-helper subset termed Th17. [13][14][15][16] gdT cells, macrophages and neutrophils are sources of IL-17 as well.…”

Blockade of Lymphocyte Chemotaxis in Visceral Graft-versus-Host Disease

“…16,17 Although studies in mice that are genetically deficient for Ccr5 have shown conflicting results, 15,17-19 genetic evidence in humans shows that certain CCR5 polymorphisms are protective against GVHD 20,21 and correlate with survival in patients undergoing allogeneic HSCT. 22 …”

C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection

“…In bone marrow transplants, CCR5 presence on CD4 + T-regulatory cells is important in prolonging graft survival (Wysocki et al, 2005). This was corroborated by a study, which showed that CCR5 genotypes with higher levels of expression have a significant survival outcome (McDermott et al, 2010). However, contrary to these findings, Bogunia-Kubik et al demonstrated that Δ32 individuals have a reduced likelihood of developing graft vs .…”