New tools for defining immune stability in long-term recipients of kidney allograft

The study of biological correlates associated with state of operational acceptance of mismatched kidney grafts years after of total interruption of immunosuppressive drugs on one side, and the growing information concerning biomarkers associated with chronic rejection may contribute to a better understanding of the status of "stable patients" years following transplantation. This understanding is crucial for guiding eventual minimalisation on weaning of immunosuppressive drugs. Recently, our laboratory has described several biological correlates with immunosuppressive drug free operational acceptance of kidney graft, including phenotypes and transcriptional alterations. Similarly, we have described a series of blood biomarkers increased (TLR4, Trib1, PSMB10) or decreased (granzyme B) in the blood of patients with chronic active rejection associated with DSA. Using these acceptance or rejection biomarkers, we screened a cohort of 164 patients presenting a highly stable clinical status at more than five years after transplantation. We show that these patients do not express the rejection associated set of biomarkers. However, according to the stringency of the analysis, few patients, of these patients under dual therapy, exhibit the operational acceptance signature (<5%). Longer follow up of these stable patients also show that a minority of them (~10%) have degraded their function with time. Grafts biopsies of these patients did not evidence chronic rejection symptom, excepted in one case but show aspecific lesions (toxicity, relapse or LAN). Despite this late degradation was not related to chronic rejection, DNAchips performed on these patients at the time of their highly stable status discriminated this outcome suggesting that an "aspecific" infl ammation status can be monitored. Collectively we hope that these data will set more scientific bases for protocols aimed at weaning CNI or other immunosuppressive drugs.

Keywords: immunosuppressive drugs, biomarkers, Transplantation