Background: The ELISPOT PRT quantifies frequencies of IFN-g-producing effector/memory T cells reactive against a panel of allogenic stimulators. In contrast to the donor-reactive ELISPOT, it does not require donor cells and therefore can be performed also in cadaveric kidney recipients awaiting transplant. Addition of IL-15 to the assay uncovers reactivity of CD28^neg memory CD8 T cells previously associated with increased risk of graft rejection (AJT 2014). Whether pre-transplant PRT+/-IL-15 is a biomarker of 2-y kidney graft function has not been carefully determined.

Methods: We performed PRT assays +/- IL-15 (IL-15 PRT) and anti-donor ELISPOT assays in 92 consecutive living (n=21) and cadaveric (n=71) kidney transplant recipients treated with thymoglobulin or basiliximab induction followed by CNI, MMF and early steroid withdrawal as maintenance. We used multivariable-regression repeated-measures linear mixed models to estimate the different time-change of eGFR between groups at 3, 6, 12, and 24-mo post-transplant, after adjusting for all potential confounders. A positive PRT was defined as >40 spots/10^5 cells against ≥50% of 8 donors (>80 spots with IL-15) based on Akaike information criterion. The threshold for positive anti-donor ELISPOT was 25 spots/2×10^5 cells, as per published studies.

Results: Absolute PRT values were highly correlated with IL-15 PRT (R:0.49; P<0.001), but there was no statistically significant correlation between PRT, or IL-15 PRT, and anti-donor ELISPOT. At baseline, 11 subjects were PRT+ (12%), [6 (7%) were IL-15 PRT+], and 61 subjects were anti-donor ELISPOT+ (66%). PRT-neg and IL-15 PRTneg subjects showed stable eGFR 3-24-mo post-transplant (-0.2mL/min, P=0.90 for PRTneg). In contrast PRT+ subjects had a significant eGFR decline (-12.8mL/mincompared with PRT-negative patients, P=0.003) [-15.2mL/min, P=0.002 with IL-15 PRT+]. Subjects positive for both PRT and anti-donor ELISPOT (N=8) had the lowest 3-mo and later eGFR (p=0.002) [P=0.012 with IL-15]. PRT levels were not associated with increased risk of AR, DGF, or histological lesions at 6-month per-protocol biopsy.

Conclusions: Pretransplant PRT and IL-15 PRT identify patients at risk for progressive graft loss independently from classic risk factors. Once validated in other cohorts, these findings will provide the rationale for using PRT screening to individualize immunosuppression.

CITATION INFORMATION: Gandolfini I, Crespo E, Baweja M, Maggiore U, Cravedi P, Heeger P, Bestard O. Pre-Transplant Panel of Reactive T Cells (PRT) as an Independent Predictor of 2-Year Kidney Graft Function. Am J Transplant. 2016;16 (suppl 3).

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