Combination of IL-1 Receptor Antagonist, IL-20 and CD40 Ligand for the Prediction of Acute Cellular Renal Allograft Rejection

Abstract

The outcome of renal transplantation is difficult to predict, even with an allograft biopsy. The aim of this study was to develop a sensitive, specific and noninvasive method for prediction of acute cellular rejection (ACR). Luminex analysis was used to determine the levels of 95 cytokines/chemokines and their soluble receptors in sera from recipients with: ACR (in the first month post-transplantation, before and during rejection, and after rejection reversal); stable allograft function; delayed graft function (DGF); pulmonary infection. Evaluation of significant differential protein expression in ACR patients compared with stable allograft controls revealed a three-analyte combination as a marker of renal transplantation outcome. The predictive value of this combination was further validated in DGF and infection groups and in a blind binary code study of 24 additional serum samples. Significant differential expression was detected in 26 proteins expressed in patients during the period preceding an ACR episode compared with stable controls. A blood test for discrimination of such patients was developed based on the simultaneous quantification of three analytes (IL-1 receptor antagonist, IL-20 and sCD40 ligand). This test exhibited 90.9 % sensitivity, 96 % specificity, a positive predictive value (PPV) of 95.2 % and a negative predictive value (NPV) of 92.3 %. Moreover, this combination allowed discrimination between patients with ACR and DGF and pulmonary infection. With further development and validation, this blood test can be used to predict ACR and direct the treatment of transplant patients in the clinic.