BACKGROUND:Belatacept is thought to disrupt the interaction between CD80/86 and CD28, thus preventing T-cell activation by blocking the co-stimulatory second signal. However, the consequences on the T-cell profile in human renal transplant cases have not been determined. METHODS: In this study, we analysed intra-graft levels of the mRNAs for Treg (FOXP3), cytotoxic CD8 T cells (Granzyme B), Th1 (INFγ, Tbet), Th2 (GATA3) and Th17 (RORγt and IL-17) in protocol biopsies obtained 12 months after renal transplantation in recipients treated with Belatacept or calcineurin inhibitor (CNI). RESULTS: Only the intra-graft abundance of FOXP3 mRNA was significantly lower (P < 0.001) in the Belatacept group than the CNI group. Conclusions. These results are in agreement with in vitro data suggesting that CD28 is a major co-stimulatory signal of both Tregs development and peripheral homeostasis but contrast with clinical trials showing a better 1-year graft function and a lower incidence of chronic allograft nephropathy in patients receiving Belatacept than patients treated with CNI. They suggest that immune benefits induced by Belatacept are not mediated by Treg expansion and that FOXP3 is not by itself a prognostic marker of long-term graft function in a non-inflammatory context. These results have to be, however, considered as preliminary since the size of our study population is limited.
RCT Entities:
BACKGROUND: Belatacept is thought to disrupt the interaction between CD80/86 and CD28, thus preventing T-cell activation by blocking the co-stimulatory second signal. However, the consequences on the T-cell profile in human renal transplant cases have not been determined. METHODS: In this study, we analysed intra-graft levels of the mRNAs for Treg (FOXP3), cytotoxic CD8 T cells (Granzyme B), Th1 (INFγ, Tbet), Th2 (GATA3) and Th17 (RORγt and IL-17) in protocol biopsies obtained 12 months after renal transplantation in recipients treated with Belatacept or calcineurin inhibitor (CNI). RESULTS: Only the intra-graft abundance of FOXP3 mRNA was significantly lower (P < 0.001) in the Belatacept group than the CNI group. Conclusions. These results are in agreement with in vitro data suggesting that CD28 is a major co-stimulatory signal of both Tregs development and peripheral homeostasis but contrast with clinical trials showing a better 1-year graft function and a lower incidence of chronic allograft nephropathy in patients receiving Belatacept than patients treated with CNI. They suggest that immune benefits induced by Belatacept are not mediated by Treg expansion and that FOXP3 is not by itself a prognostic marker of long-term graft function in a non-inflammatory context. These results have to be, however, considered as preliminary since the size of our study population is limited.
Authors: Esilida Sula Karreci; Siawosh K Eskandari; Farokh Dotiwala; Sujit K Routray; Ahmed T Kurdi; Jean Pierre Assaker; Pavlo Luckyanchykov; Albana B Mihali; Omar Maarouf; Thiago J Borges; Abdullah Alkhudhayri; Kruti R Patel; Amr Radwan; Irene Ghobrial; Martina McGrath; Anil Chandraker; Leonardo V Riella; Wassim Elyaman; Reza Abdi; Judy Lieberman; Jamil Azzi Journal: JCI Insight Date: 2017-11-02
Authors: Gretchen N de Graav; Dennis A Hesselink; Marjolein Dieterich; Rens Kraaijeveld; Willem Weimar; Carla C Baan Journal: PLoS One Date: 2016-02-26 Impact factor: 3.240
Authors: Evelyn Katy Alvarez Salazar; Arimelek Cortés-Hernández; Germán Rodrigo Alemán-Muench; Josefina Alberú; Jesús R Rodríguez-Aguilera; Félix Recillas-Targa; Victoria Chagoya de Sánchez; Eric Cuevas; Eduardo Mancilla-Urrea; María Pérez García; Guillermo Mondragón-Ramírez; Mario Vilatobá; Ian Bostock; Erick Hernández-Méndez; David De Rungs; Eduardo A García-Zepeda; Gloria Soldevila Journal: Front Immunol Date: 2017-03-03 Impact factor: 7.561
Authors: Marieke van der Zwan; Carla C Baan; Robert B Colvin; Rex N Smith; Rebecca A White; Dorothy Ndishabandi; Alex L Nigg; Thierry P P van den Bosch; Gretchen N de Graav; Marian C Clahsen-van Groningen; Dennis A Hesselink Journal: Transplant Direct Date: 2018-12-20