Faculty Collaboration Database

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

Date

02/16/2019

Pubmed ID

30768834

DOI

10.1111/ajt.15315

Scopus ID

2-s2.0-85062984866 (requires institutional sign-in at Scopus site)   80 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.

Author List

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

Author

Matthew Cooper MD Chief, Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antiviral Agents
Cytomegalovirus Infections
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immediate-Early Proteins
Immune System
Immunity, Cellular
Kaplan-Meier Estimate
Kidney Failure, Chronic
Kidney Transplantation
Male
Middle Aged
Peptides
Predictive Value of Tests
Prospective Studies
ROC Curve
T-Lymphocytes
Treatment Outcome
Viral Matrix Proteins
Young Adult