A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients

Am J Transplant. 2019 Sep;19(9):2505-2516. doi: 10.1111/ajt.15315. Epub 2019 Mar 15.


T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV-specific peptide-based enzyme-linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN-γ) binding spot-forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early-1 (IE-1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R-] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92-360) posttransplant. A cutoff value of >40 sfu/2.5 × 105 cells for either IE-1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P < .0001 for pp65). Time to CMV event post-EOP was significantly greater in those with sfu >40 at EOP (P < .0001). In this large, multicenter trial of kidney transplant recipients, we show that an assessment of CMV-specific immunity using a novel ELISPOT assay is able to predict protection from CMV infection.

Keywords: T cell biology; clinical research/practice; infection and infectious agents - viral: cytomegalovirus (CMV); infectious disease; kidney transplantation/nephrology.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus Infections / complications*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immediate-Early Proteins / immunology
  • Immune System
  • Immunity, Cellular*
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Peptides / chemistry
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • T-Lymphocytes / cytology
  • Treatment Outcome
  • Viral Matrix Proteins / immunology
  • Young Adult


  • Antiviral Agents
  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Peptides
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa