Impact of maintenance immunosuppressive regimens--balance between graft protective suppression of immune functions and a near physiological immune response.
Author(s): Weimer R, Deisz S, Dietrich H, Renner F, Bodeker RH, Daniel V, Kamali-Ernst S, Ernst W, Padberg W, Opelz G
Affiliation(s): Department of Internal Medicine, University of Giessen, Klinikstrasse 36, Giessen, Germany. rolf.weimer@innere.med.uni-giessen.de
Publication date & source: 2011-06, Transpl Int., 24(6):596-609. Epub 2011 Mar 14.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
The Symphony study showed superior 1-year kidney graft outcome in patients on immunosuppression with tacrolimus/mycophenolate mofetil (Tacr/MMF). To analyze whether differences in clinical outcome between maintenance regimens may be explained by their impact on clinically relevant immune parameters, we assessed CD4 helper activity, immunoglobulin-secreting cell (ISC) formation, neopterin, sCD30, and intracellular cytokine production in a prospective study in 77 renal transplant recipients treated with cyclosporine A/azathioprine (CsA/Aza), CsA/MMF, Tacr/Aza or Tacr/MMF at 2 years post-transplant. Tacr- compared with CsA-based immunosuppression was independently associated with increased IL-2 (P<0.0001, CD4 cells; P=0.014, CD8 cells) and CD4 cell IL-4 responses (P=0.046; stepwise logistic regression) resulting in physiological responses in Tacr/Aza patients as compared with 25 healthy controls. MMF versus Aza treatment was proven to be an independent variable associated with suppression of CD4 cell IL-10 responses (P=0.008), B-cell IL-6R expression (P<0.0001) and ISC formation [P=0.020, staphylococcus cowan strain I (SAC I); P=0.021, pokeweed mitogen (PWM)]. Our data suggest that Tacr/MMF had the most effective impact on graft protective Th2 responses (enhanced CD4 cell IL-4 by Tacr, decreased CD4 cell IL-10 responses by MMF) and suppression of B-cell functions (MMF), whereas Tacr/Aza was associated with physiological IL-2 and IL-4 and stronger humoral responses which may reduce the risk of infectious disease complications. (c) 2011 The Authors. Transplant International (c) 2011 European Society for Organ Transplantation.
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