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Prospective, Multi-Center Observational Study of Cell-Mediated Immunity for Cytomegalovirus Infection in Kidney Transplant Recipients

D. Kumar,1 P. Chin-Hong,2 L. Kayler,3 D. Wojciechowski,4 A. Limaye,5 O. Gaber,6 S. Ball,7 A. Mehta,8 T. Blanchard,9 C. Kotton.4

1UHN, Toronto, Canada
2UCSF, San Francisco
3ECMC, Buffalo
4MGH, Boston
5UOWMC, Seattle
6WCMC, Houston
7UHB, Birmingham, United Kingdom
8EmoryU, Atlanta
9Oxford Diag, Marlborough.

Meeting: 2018 American Transplant Congress

Abstract number: 187

Keywords: Immunodominant peptide, Infection, T cell reactivity, Viral therapy

Session Information

Date: Monday, June 4, 2018

Session Name: Concurrent Session: CMV: Bench to Bedside

Session Time: 2:30pm-4:00pm

 Presentation Time: 3:18pm-3:30pm

Location: Room 608/609

Related Abstracts
  • Association of Cytomegalovirus-Specific T Cell-Mediated Immunity with the Risk of CMV Infection Occurrence in Kidney Transplant Recipients.
  • A Prospective Observational Study to Evaluate Use of a Panel of Reactive T Cell (PRT) Assay as a Pre-Transplant Marker of Rejection in Kidney Transplant Recipients.

Background:

T-cell-mediated immunity (CMI) is crucial for the control of CMV infection post-transplant. We evaluated a novel EliSpot assay to determine whether CMI results could predict subsequent CMV events.

Methods:

Adult kidney transplant recipients were enrolled at 43 centers in U.S., Canada, and U.K. An EliSpot assay (T.Spot.CMV, Oxford Diagnostics) was used to enumerate IFNγ binding spot forming units (sfu) after stimulation of PBMCs with an overlapping peptide pool of CMV pp65 and IE-1 proteins. Testing was done at end of antiviral prophylaxis (EOP) and 1,2,3,4,6 months post-EOP. The primary outcome was a CMV event in the first post-transplant year, defined as site-determined viremia requiring antiviral therapy.

Results:

We enrolled 571 KTRs (277 D+/R- and 294 R+) with a mean age of 52 ± 15.5 yrs; majority of patients were male (62%). Of these, 223 (39.1%) and 348 (60.9%) received 3 and 6 months of prophylaxis respectively. In patients who were eligible for analysis (n=372), CMV events occurred in 44 (11.8%) (37/168 (21.9%) D+/R- and 7/204 (3.4%) R+) after EOP at a median 64 days (range 1-240 days) post-prophylaxis. Using ROC curve analysis, we derived a cutoff of >50 sfu/2×105 PBMC for either IE-1 or pp65 as a threshold for positivity with good sensitivity and specificity for prediction of CMV events. At EOP 23/168 (13.7%) D+/R- were positive and 147/204 (72.1%) R+ were positive. In the total cohort (n=372), CMV events were significantly lower in CMI positive vs. negative patients (2.9% vs. 17.6%, p<0.0001). This was primarily driven by the R+ group where a positive CMI reduced the risk of a CMV event (OR 0.13, 95%CI: 0.049 – 0.33). Time to CMV event post-EOP was significantly greater in those with positive CMI (log-rank p<0.0001). Similar predictive values for subsequent CMV events were found for CMI measurements at 1 and 2 months post-prophylaxis (p<0.0001 and p=0.062 respectively).

Conclusion:

In the largest cohort of KTRs to date, we show that a standardized assessment of CMV-specific CMI using a novel EliSpot assay has predictive value for clinically significant CMV infection.

CITATION INFORMATION: Kumar D., Chin-Hong P., Kayler L., Wojciechowski D., Limaye A., Gaber O., Ball S., Mehta A., Blanchard T., Kotton C. Prospective, Multi-Center Observational Study of Cell-Mediated Immunity for Cytomegalovirus Infection in Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Kumar D, Chin-Hong P, Kayler L, Wojciechowski D, Limaye A, Gaber O, Ball S, Mehta A, Blanchard T, Kotton C. Prospective, Multi-Center Observational Study of Cell-Mediated Immunity for Cytomegalovirus Infection in Kidney Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/prospective-multi-center-observational-study-of-cell-mediated-immunity-for-cytomegalovirus-infection-in-kidney-transplant-recipients/. Accessed December 5, 2019.

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