Risk prediction of CMV reactivation after allogeneic stem cell transplantation using five non-HLA immunogenetic polymorphisms

Abstract

Despite advances in the understanding of the pathophysiology of cytomegalovirus (CMV) infection, it remains as one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to determine the genotype of cytokines and chemokines in donor and recipient and their association with CMV reactivation. Eighty-five patients receiving an allo-HSCT from an HLA-identical sibling donor were included in the study. Fifty genes were selected for their potential role in the pathogenesis of CMV infection. CMV DNAemia was evaluated until day 180 after allo-HSCT. CMV reactivation was observed in 51/85 (60%) patients. Of the 213 genetic variants selected, 11 polymorphisms in 7 different genes (CXCL12, IL12A, KIR3DL1, TGFB2, TNF, IL1RN, and CD48) were associated with development or protection from CMV reactivation. A predictive model using five of such polymorphisms (CXCL12 rs2839695, IL12A rs7615589, KIR3DL1 rs4554639, TGFB2 rs5781034 for the recipient and CD48 rs2295615 for the donor) together with the development of acute GVHD grade III/IV improved risk stratification of CMV reactivation. In conclusion, the data presented suggest that the screening of five polymorphisms in recipient and donor pre-transplantation could help to predict the individual risk of CMV infection development after HLA-identical allo-HSCT.

Characterization of recurrent cytomegalovirus reactivations post allogenic stem cell transplantation in a population with high seropositivity

“…Onset of CMV reactivation is typically reported within 28 to 72 days after transplantation; affecting 40–60% of bone marrow allogeneic transplant recipients and may progress to severe CMV-related diseases [ 7 – 9 ]. It is worth mentioning that variation in CMV reactivation definition among clinical studies may contribute to the wide ranges of CMV reactivation rates seen in literature.…”

Cytokine and Chemokine Secretome and Risk of CMV Infection Following Discontinuation of Valganciclovir Prophylaxis

“…Often considered a homeostatic chemokine, inflammatory activities have been attributed to SDF-1 (CXCL12) ( 7 ). Polymorphisms in the CXCL12 gene are associated with the occurrence of CMV reactivation after allogeneic hematopoietic stem cell transplantation ( 8 ), whereas elevated plasma levels identify poor immune reconstitution in HIV patients ( 9 ). SDF1 mainly signals via the CXCR4 receptor, and it has been shown that CMV enhances SDF-1/CXCR4 signaling during infection through the product of the UL111A gene (which encodes a viral ortholog of human IL-10) ( 10 ).…”