ATC abstract presentation: Alemtuzumab Induction and Belatacept-Based Immunosuppression in Renal Transplant Recipients: Peripheral Dynamics of T and B cell Populations with Potential Regulatory Signatures.
In Monday’s session on Novel immunosuppressive agents, Dr. Xu of Emory University, presented his center’s data on using a combination of belatacept with sirolimus after alemtuzumab induction in kidney transplant recipients. The focus of the presentation was immune repopulation in patients treated with this protocol. The concept is an interesting one, as alemtuzumab has been used as an agent to significantly reduce the risk of rejection while allowing long term minimization of immunosuppression. Belatacept has been found to improve GFR compared to calcineurin inhibitors albeit at a higher rejection rate. The combination of belatacept and sirolimus has also been suggested to lead to a tolerogenic state in primates. The combination of these 3 agents then makes sense as a protocol to reduce the risk of early rejection while potentially creating long term immune hypoalloresponsivness.
To test their hypothesis, the authors evaluated the T and B cell repertoire after alemtuzumab induction and out to 2 years post transplant. They found an expected profound T and B cell depletion after induction. Subsequently they found that FOXP3 T regulatory cells increased during repopulation above baseline values at 1 yr post transplant which later declined to baseline (18 mo post transplant). B cells revealed a rapid repopulation with a higher than baseline number of naive, regulatory and transitional cells while memory B cells did not return to baseline.
The authors conclude that their data supports antigen specific hyporesponsivness induced by the combination of alemtuzumab induction with belatacept/sirolimus maintenance. Long-term clinical follow up should reveal if the change in cell repertoire truly translates into better outcome.
Post written by Dr. Vinay Nair, eAJKD Advisory Board member.
Check out all of eAJKD’s coverage of the 2013 American Transplant Congress.