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

Abstract

The advent of interferon (IFN)-γ release assays (IGRAs) to quantify cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-IMC) has represented a major step in the effort to individualize preventive strategies after kidney transplantation (KT). We have recently shown, however, that the QuantiFERON ® -CMV (QTF-CMV) assay at the time of discontinuation of antiviral prophylaxis exhibits suboptimal accuracy (sensitivity of 77.4%, specificity of 34.3%, positive [PPV] and negative predictive values [NPV] of 64.1% and 50.0%, respectively) to predict protection among KT recipients that had received induction therapy with antithymocyte globulin (ATG) (1). The assessment of IFN-γ production by IGRAs is aimed at recapitulating the Th1-polarized CMV-IMC. Nevertheless, CD4 + T-cell functions are also mediated through other lymphocyte subsets (such as Th2 or Th17), each of which secretes a distinct cytokine profile. A comprehensive profiling of the cytokine and chemokine responses upon CMV-specific stimulation may improve the performance of the QTF-CMV assay (2).Samples collected from patients recruited in a previous study were used for the present analysis (1). Consecutive CMV-seropositive KT recipients receiving ATG induction at our institution between April 2015 and June 2018 underwent CMV-CMI monitoring by the QTF-CMV assay at months 2, 3, 4 and 5. A 3-month course of valganciclovir prophylaxis was scheduled in all of them. The QTF-CMV assay was performed according to the manufacturer's instructions. We selected those samples obtained at the time of discontinuation of prophylaxis (±3 weeks). The following 27 cytokines and chemokines were measured in stimulated ("CMV tube") and unstimulated ("nil tube") plasma samples by means of analyte-specific capture beads coated with target-specific capture antibodies in a

Comprehensive Analysis of Soluble Mediator Profiles in Congenital CMV Infection Using an MCMV Model

“…While cytokines have been measured in sera and brain tissue of MCMV-infected newborn mice, most researchers used ELISA-based protein concentration assays for selected targets or detection based on RNA levels ( Table 2 ). Regarding human samples, the analysis of blood secretome after CMV-specific stimulation was previously investigated using a multiplex detection technique [ 63 ]. However, these samples were from adult transplantation patients, whereas our research strictly aims to profile the expression of soluble immune mediators in congenitally infected tissues.…”