Anft Moritz, Zgoura Panagiota, Skrzypczyk Sarah, Dürr Michael, Viebahn Richard, Westhoff Timm H, Stervbo Ulrik, Babel Nina
Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.
Clinic for Internal Medicine, St. Anna Hospital Herne, Herne, Germany.
Front Transplant. 2024 Sep 25;3:1405070. doi: 10.3389/frtra.2024.1405070. eCollection 2024.
LCP-Tacro [LCPT], a novel once-daily, extended-release formulation of tacrolimus, has a reduced C with comparable AUC exposure, requiring a ∼30% dose reduction in contrast to immediate-release tacrolimus (IR-Tac). Once-daily LCPT in 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 analyze 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 fl ow cytometry. Additionally, we analyzed T cells by assessing third-party antigens (Tetanus Diphtheria, 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.
LCP-Tacro（LCPT）是一种新型的他克莫司每日一次缓释制剂，其谷浓度（C）降低，但曲线下面积（AUC）暴露相当，与即释型他克莫司（IR-Tac）相比，剂量需降低约30%。肾移植中每日一次的LCPT与IR-Tac具有相当的疗效和安全性，在生物利用度和吸收方面具有优势。本研究旨在分析从IR-Tac转换为LCPT对T细胞和B细胞表型及功能的影响。
本观察性前瞻性研究纳入了16例接受三联标准免疫抑制治疗且移植肾功能稳定、正在从IR-Tac转换为LCPT的肾移植患者。我们使用多参数流式细胞术测量了主要免疫细胞类型，并对患者在从IR-Tac转换为LCPT之前、转换后4周和8周时的B细胞、树突状细胞和T细胞（包括调节性T细胞）进行了深入表征。此外，我们通过评估第三方抗原（破伤风-白喉，TD）反应性T细胞来分析T细胞，可通过破伤风疫苗再刺激进行分析。
总体而言，我们发现转换为LCPT后，大多数免疫细胞群体没有显著变化，少数细胞群体出现短暂的数量增加。因此，转换后4周，患者体内可检测到更多的调节性T细胞，且从记忆性调节性T细胞向初始调节性T细胞有显著转变。此外，我们发现从IR-Tac转换为LCPT后4周，B细胞出现短暂扩增。更换为LCP-他克莫司后，其他基本免疫细胞类型的百分比没有变化，抗原反应性T细胞也没有改变。
在此，我们首次展示了肾移植患者在从IR-Tac转换为LCPT治疗过程中免疫系统的变化。虽然大多数免疫细胞群体的表型和功能特征没有改变，但我们可以观察到从IR-Tac转换为LCTP后外周血中调节性T细胞的短暂扩增，这可能会进一步增强整体免疫抑制效果。
