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

2 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cytomegalovirus Infections
Cytomegalovirus
Cellular Immunity
Multicenter Studies
Observational Studies
Kidney
Antiviral Agents
Immunity
Enzyme-Linked Immunosorbent Assay
Immediate-Early Proteins
Immunosorbents
Peptides
Phosphoproteins
Transplant Recipients
Interferon-gamma
Transplantation
Tissue Donors
T-Lymphocytes
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients. / Kumar, Deepali; Chin-Hong, Peter; Kayler, Liise; Wojciechowski, David; Limaye, Ajit P.; Osama Gaber, A.; Ball, Simon; Mehta, Aneesh K.; Cooper, Matthew; Blanchard, Ted; MacDougall, James; Kotton, Camille N.

In: American Journal of Transplantation, Vol. 19, No. 9, 01.01.2019, p. 2505-2516.

Research output: Contribution to journalArticle

Kumar, D, Chin-Hong, P, Kayler, L, Wojciechowski, D, Limaye, AP, Osama Gaber, A, Ball, S, Mehta, AK, Cooper, M, Blanchard, T, MacDougall, J & Kotton, CN 2019, 'A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients', American Journal of Transplantation, vol. 19, no. 9, pp. 2505-2516. https://doi.org/10.1111/ajt.15315
Kumar, Deepali ; Chin-Hong, Peter ; Kayler, Liise ; Wojciechowski, David ; Limaye, Ajit P. ; Osama Gaber, A. ; Ball, Simon ; Mehta, Aneesh K. ; Cooper, Matthew ; Blanchard, Ted ; MacDougall, James ; Kotton, Camille N. / A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients. In: American Journal of Transplantation. 2019 ; Vol. 19, No. 9. pp. 2505-2516.
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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.",
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AU - Ball, Simon

AU - Mehta, Aneesh K.

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