Identification of a gene expression profile associated with operational tolerance among a selected group of stable kidney transplant patients

Abstract

Despite their utility, immunosuppressive treatments have numerous side effects, including infectious complications, malignancies and metabolic disorders, all of which contribute to long-term graft loss. In addition to the development of new pharmaceutical products with reduced toxicity and more comfortable modes of administration, tailoring immunosuppression according to the immune status of each patient would represent a significant breakthrough. Gene expression profiling has been shown to be a clinically relevant monitoring tool. In this paper, we have assessed the overall long-term kidney transplant outcome and attempted to identify operationally tolerant-like patients among recipients with stable clinical status at least 5 years post-transplantation. We thus measured a combination of noninvasive blood biomarkers of operational tolerance in a cohort of 144 stable patients and showed that only 3.5% exhibited a gene expression profile of operational tolerance, suggesting that such a profile can be detected under immunosuppressive therapy but that its frequency is low in kidney transplant recipients when compared with liver transplant recipients. We suggest that a rational approach to patient selection, based on a combination of clinical and biological characteristics, may help to provide a safer method for identification of patients potentially suitable for immunosuppressive drug weaning procedures.