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

Deepali Kumar, Peter Chin-Hong, Liise Kayler, David Wojciechowski, Ajit P. Limaye, A. Osama Gaber, Simon Ball, Aneesh K. Mehta, Matthew Cooper, Ted Blanchard, James MacDougall, Camille N. Kotton

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2505-2516
Number of pages12
JournalAmerican Journal of Transplantation
Volume19
Issue number9
DOIs
StatePublished - Jan 1 2019

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Kumar, D., Chin-Hong, P., Kayler, L., Wojciechowski, D., Limaye, A. P., Osama Gaber, A., Ball, S., Mehta, A. K., Cooper, M., Blanchard, T., MacDougall, J., & Kotton, C. N. (2019). A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients. American Journal of Transplantation, 19(9), 2505-2516. https://doi.org/10.1111/ajt.15315