CONICET | Buscador de Institutos y Recursos Humanos

Belatacept is a CTLA4-Ig fusion protein that contain the extracellulardomain of CTLA-4 coupled to the Fc fragment of a human immunoglobulin G1 antibody. It blocks the costimulatory signals mediated by B7-CD28 and it has been used in kidney transplant patients.However, the incidence of adverse clinical events mainly in early,but not late post-transplantation such as an increased rate of acuterejection precludes the use of Belatacept in all transplant patients.The aim of this study was to compare the cell immunophenotypingin kidney transplant patients treated with Belatacept from the begining (de novo) with those converted to Belatacept from calcineurininhibitors. For both groups of patients, the immunophenotyping wereperformed after at least 9 months of the introduction of Belataceptto the immunosuppresive regimen. Peripheral blood mononuclearcells were isolated from 30 transplant patients (16 de novo). Therewas not statistically significant difference in patients age, BMI, transplantation time, leukocytes numbers between both groups. Severalcostimulatory molecules and their ligands were measured on monocytes and lymphocytes by flow cytometry. There was not statisticallydifferences on monocytes expression of CD80, CD86, B7H2, CD40and PD-L1 between both groups of patients. However, there was aslightly higher expression of SLAM (p=0.05) on monocytes derivedfrom converted patients. On T cells, de novo patients had higher levels of CD27 (p=0.01) and CD28 (p=0.05) but lower of ICOS (p=0.03)compared with converted patients. Then, we assessed the lymphoproliferation capacity of PBMC from de novo and converted group ofpatients. Regardless of the group of patients, proliferation was thesame in response to PHA but de novo showed higher allostimulatory capacity than converted patients (p=0.02). Overall these resultsshow that Belatacept converted-patients has a different leukocytesimmunophenotype than de novo and this could affect the allostimulatory capacity