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ORIGINAL RESEARCH article
Front. Transplant.
Sec. Immunosuppression
Volume 3 - 2024 |
doi: 10.3389/frtra.2024.1405070
Effects of switching from twice-daily tacrolimus to once-daily extended-release meltdose tacrolimus on cellular immune response
Provisionally accepted- 1 Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
- 2 St. Anna Hospital, Herne, Germany
- 3 Charité Center for Global Health, Charité Universitätsmedizin Berlin, Berlin, Baden-Württemberg, Germany
- 4 Department for Surgery, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, North Rhine-Westphalia, Germany
- 5 Berlin-Brandenburg Center for Regenerative Therapies, Charité Medical University of Berlin, Berlin, Baden-Wurttemberg, Germany
LCP-Tacro [LCPT], a novel once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction in contrast to immediate-release tacrolimus (IR-Tac). Once-daily LCPT in de novo kidney transplantation has a comparable efficacy and safety profile to that of IR-Tac with advantages in bioavailability and absorption. The present investigation intends to analyse the effects of conversion from IR-Tac to LCPT on phenotype and function of T-cells and B-cells. 16 kidney transplant patients treated by triple standard immunosuppression with a stable graft function undergoing a switch from IR-Tac to LCPT were included in this observational prospective study. We measured the main immune cell types and performed an in-depth characterization of B cell, dendritic cells and T cells including regulatory T cells of the patients before, 4 and 8 weeks after IR-Tac to LCPT conversion using multi-parameter flow cytometry. Additionally, we analysed T cells by assessing third-party antigens (Tetanus Diphteria, TD)-reactive T cells, which could be analyzed by restimulation with tetanus vaccine. Overall, we found no significant alterations following LCPT conversion for the most immune cell populations with a few cell populations showing transient quantitative increase. Thus, 4 weeks after conversion, more regulatory T cells could be measured in the patients with a significant shift from memory to naïve Tregs. Furthermore, we found a transient B cell expansion 4 weeks after conversion from IR-Tac to LCPT. There were no changes in the percentage of other basic immune cell types and the antigen-reactive T cells were also not altered after changing the medication to LCP-tacrolimus Here, we demonstrate first insights into the immune system changes occurred under IR-Tac to LCPT conversion therapy in kidney transplant patients. While phenotypic and functional characteristics of the most immune cell populations did not change, we could observe an a transient expansion of regulatory T cells in peripheral blood following IR-Tac to LCTP conversion, which might additionally contribute to the overall immunosuppressive effect.
Keywords: Immunity, Immunesupression, Kidney Transplantation, Tacrolimus, T cells
Received: 22 Mar 2024; Accepted: 06 Sep 2024.
Copyright: © 2024 Anft, Zgoura, Skrzypczyk, Dürr, Viebahn, Westhoff, Stervbo and Babel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Nina Babel, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
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