Signatures of kidney transplant rejection and acceptance

Three new reports describe biomarkers that identify either kidney transplant recipients likely to maintain excellent and stable allograft function in the absence of immunosuppressive drugs or those at risk of losing their transplants. Peter Heeger and Bernd Schröppel, at Mount Sinai School of Medicine, New York, describe in an accompanying commentary, the importance of these studies and how they might impact the management of patients in the clinic to provide a more personalized treatment regimen. The most common solid organ transplant procedure performed in the US is kidney transplantation for the treatment of end-stage kidney disease. Transplant recipients must take immunosuppressive drugs for the rest of their lives to prevent rejection of their transplanted kidney, and this has serious negative health consequences. Furthermore, these drugs do not prevent either late-stage rejection of the transplant or transplant failure. To improve long-term outcomes it would be helpful if physicians could determine whether a patient was at risk of losing their transplanted kidney or whether a patient's immune system was sufficiently tolerant of the transplanted kidney that they could stop taking their immunosuppressive drugs.

Two teams of researchers — one led by Maria Hernandez-Fuentes, at King's College London, United Kingdom, and the other led by Kenneth Newell, at Emory University, Atlanta, Laurence Turka, at Beth Israel Deaconess Medical Center, Boston, and Vicki Seyfert-Margolis, at Immune Tolerance Network, Bethesda, — independently identified and studied rare kidney transplant recipients who have excellent and stable graft function despite no longer taking their immunosuppressive drugs. Both groups identified a signature that was associated with this outcome and both signatures were indicative of immune cells known as B cells having a beneficial role. In contrast, in the third study, researchers led by Philip Halloran, at the University of Alberta, Edmonton, identified in patients who had received their kidney transplant more than a year prior to the analysis a molecular signature indicative of future organ failure. All three groups hope that if validated in further studies their signatures might help physicians design more personalized treatment regimens for kidney transplant recipients, for example identifying those that might be candidates for drug-weaning protocols.

Source: Journal of Clinical Investigation