BACKGROUND: Recently introduced immunosuppressive drugs are more potent to control graft rejection, but current concerns are raised regarding their potential to increase long-term neoplastic and infectious complications. Considering the role of B, T, or natural killer (NK) lymphocyte in controlling alloreactive, anti-infectious, and antitumoral immune responses, we compared the impact of two immunosuppressive regimens on lymphocyte subsets one year following kidney transplant. METHODS: Multivariate regression analysis of variables affecting lymphocyte subset counts was retrospectively performed on 91 kidney-transplanted patients, analyzed before graft, at day 15 and 1-year postgraft. These patients were included in a randomized prospective open trial comparing tacrolimus/mycophenolate mofetil (FK/MMF) versus cyclosporine/azathioprine (CSA/Aza), both used in association with rabbit antithymocyte globulines (rATG) induction and prednisone. RESULTS: Fifteen days postgraft, severe T and NK lymphocyte depletion were observed in all patients, while B cell counts were selectively higher in the FK/MMF group as compared to before graft. One-year posttransplant, NK cell counts and NK cell cytotoxicity was significantly higher in patients receiving FK/MMF therapy, as compared to CSA/Aza. Cytomegalovirus (CMV) infection during the first year posttransplant was also associated to higher NK, CD8, and CD4CD8 T cell counts at month 12. CONCLUSIONS: In addition to its higher potential in preventing graft rejection, we show that after one year of transplant, FK/MMF better preserves NK innate immune effector cells and their cytotoxic potential. These data prompt to further evaluate the role of NK cells in relation to antiviral and tumoral surveillance of transplanted patients, which are common complications of long-term immunosuppression.
RCT Entities:
BACKGROUND: Recently introduced immunosuppressive drugs are more potent to control graft rejection, but current concerns are raised regarding their potential to increase long-term neoplastic and infectious complications. Considering the role of B, T, or natural killer (NK) lymphocyte in controlling alloreactive, anti-infectious, and antitumoral immune responses, we compared the impact of two immunosuppressive regimens on lymphocyte subsets one year following kidney transplant. METHODS: Multivariate regression analysis of variables affecting lymphocyte subset counts was retrospectively performed on 91 kidney-transplanted patients, analyzed before graft, at day 15 and 1-year postgraft. These patients were included in a randomized prospective open trial comparing tacrolimus/mycophenolate mofetil (FK/MMF) versus cyclosporine/azathioprine (CSA/Aza), both used in association with rabbit antithymocyte globulines (rATG) induction and prednisone. RESULTS: Fifteen days postgraft, severe T and NK lymphocyte depletion were observed in all patients, while B cell counts were selectively higher in the FK/MMF group as compared to before graft. One-year posttransplant, NK cell counts and NK cell cytotoxicity was significantly higher in patients receiving FK/MMF therapy, as compared to CSA/Aza. Cytomegalovirus (CMV) infection during the first year posttransplant was also associated to higher NK, CD8, and CD4CD8 T cell counts at month 12. CONCLUSIONS: In addition to its higher potential in preventing graft rejection, we show that after one year of transplant, FK/MMF better preserves NK innate immune effector cells and their cytotoxic potential. These data prompt to further evaluate the role of NK cells in relation to antiviral and tumoral surveillance of transplanted patients, which are common complications of long-term immunosuppression.
Authors: Olivier Morteau; Samkeliso Blundell; Aron Chakera; Sophia Bennett; Charita M Christou; Philip D Mason; Richard J Cornall; Christopher A O'Callaghan Journal: PLoS One Date: 2010-10-12 Impact factor: 3.240
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