Pretransplant Donor-specific IFN gamma ELISPOT as a Predictor of Graft Rejection: A Diagnostic Test Accuracy Meta-analysis

Abstract

Background. Pretransplant interferon-gamma enzyme-linked immunospot (IFN-gamma ELISPOT) has been proposed as a tool to quantify alloreactive memory T cells and estimate the risk of acute rejection (AR) after kidney transplantation, but studies have been inconclusive so far. We performed a meta-analysis to evaluate the association between pretransplant IFN-gamma ELISPOT and AR and assess its predictive accuracy at the individual level. Methods. We estimated the pooled summary of odds ratio for AR and the joined sensitivity and specificity for predicting AR using random-effects and hierarchical summary receiver-operating characteristic models. We used meta-regression models with the Monte Carlo permutation method to adjust for multiple tests to explain sensitivity and specificity heterogeneity across studies. The meta-analytic estimates of sensitivity and specificity were used to calculate positive and negative predictive values across studies. Results. The analysis included 12 studies and 1181 patients. IFN-gamma ELISPOT was significantly associated with increased AR risk (odds ratio: 3.29; 95% confidence interval (CI), 2.34-4.60); hierarchical summary receiver operating characteristic jointly estimated sensitivity and specificity values were 64.9% (95% CI, 53.7%-74.6%) and 65.8% (95% CI, 57.4%-73.5%), respectively, with moderate heterogeneity across studies. After adjusting for multiple testing, meta-regression models showed that thymoglobulin induction, recipient black ethnicity, living versus deceased donors, and geographical location did not affect sensitivity or specificity. Because of the varying AR incidence of the studies, positive and negative predictive values ranged between 16%-60% and 70%-95%, respectively. Conclusions. Pretransplant IFN-gamma ELISPOT is significantly associated with increased risk of AR but provides suboptimal predictive ability at an individual level. Prospective randomized clinical trials are warranted.