Clinical validation of a novel enzyme-linked immunosorbent spot assay-based in vitro diagnostic assay to monitor cytomegalovirus-specific cell-mediated immunity in kidney transplant recipients: a multicenter, longitudinal, prospective, observational study

Transpl Int. 2018 Apr;31(4):436-450. doi: 10.1111/tri.13110. Epub 2018 Jan 16.

Abstract

Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of CMV reactivation and associated complications in solid-organ transplantation. Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T-Track® CMV, a novel IFN-γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE-I CMV proteins, to monitor CMV-CMI following kidney transplantation. A prospective longitudinal multicenter study was conducted in 86 intermediate-risk renal transplant recipients. CMV-CMI, CMV viral load, and clinical complications were monitored over 6 months post-transplantation. Ninety-five percent and 88-92% ELISpot assays were positive pre- and post-transplantation, respectively. CMV-specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state. Interestingly, median pp65-specific response was ninefold higher in patients with self-clearing viral load compared to antivirally treated patients prior to first viral load detection (P < 0.001), suggesting that reactivity to pp65 represents a potential immunocompetence marker. Altogether, T-Track® CMV is a highly sensitive IFN-γ ELISpot assay, suitable for the immunomonitoring of CMV-seropositive renal transplant recipients, and with a potential use for the risk assessment of CMV-related clinical complications (ClinicalTrials.gov Identifier: NCT02083042).

Keywords: CMV-specific cell-mediated immunity; IFN-γ ELISpot; cytomegalovirus; immunomonitoring; in vitro diagnostic; kidney or renal transplantation.

Publication types

  • Multicenter Study
  • Observational Study
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / immunology
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / virology
  • Humans
  • Immunity, Cellular*
  • Immunosuppressive Agents
  • Kidney Transplantation
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Opportunistic Infections
  • Phosphoproteins / immunology*
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / immunology
  • Prospective Studies
  • Viral Matrix Proteins / immunology*
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa

Associated data

  • ClinicalTrials.gov/NCT02083042