Abstract
Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.
Highlights
Type III interferons IFNs), including IFNλ1, IFNλ2 and IFNλ3 known as IL29, IL28A and IL28B respectively, are thought to display antiviral and immunomodulatory properties in vivo, which may partially overlap those exerted by type I IFNs. [2,3] Type I and Type III IFNs both generate an antiviral state by triggering the JAK-STAT pathway, upregulating the expression of IFN stimulated genes. [2,3]
Several lines of evidence suggest that IL28B/IFNλ4 Single Nucleotide Polymorphisms (SNPs) might play a role in the control of CMV infection in Allo-stem cell transplantation (SCT) and solid organ cells transplant recipients [1,17,18]; to date no data are available in autologous stem cells transplantation (Auto- SCT) setting
The current study was aimed at investigating factors that may be involved in CMV reactivation and whether the rs12979860 IFNλ3 polymorphism and the relative rs368234815 IFNλ4 genotype may have any effect on the incidence rate and outcome of active CMV infection in Auto-SCT
Summary
Linkage disequilibrium (LD) between IFNλ4-ΔG, which creates IFNλ4 protein, and the (unfavorable) IFNλ3 rs12979860-T allele was demonstrated to be very high among Caucasians (>0.9) [10] This means that these variants are always inherited together making sometime difficult to determine which one is more strongly associated with the outcome and, more likely to be causal. Despite there is strong evidence that genotypes for rs12979860 and IFNλ4- TT/ΔG may play a role in other infections [11,12,13,14,15,16], their relevance in CMV reactivation following stem cell transplantation is still debated. Several lines of evidence suggest that IL28B/IFNλ4 SNPs might play a role in the control of CMV infection in Allo-SCT and solid organ cells transplant recipients [1,17,18]; to date no data are available in autologous stem cells transplantation (Auto- SCT) setting. The current study was aimed at investigating factors that may be involved in CMV reactivation and whether the rs12979860 IFNλ3 polymorphism and the relative rs368234815 IFNλ4 genotype may have any effect on the incidence rate and outcome of active CMV infection in Auto-SCT
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