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<p>Tacrolimus (TAC) is a pivotal immunosuppressant used to prevent graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). However, because lymphocytes express P-glycoprotein (P-gp), which actively effluxes TAC, blood TAC concentrations do not necessarily reflect intracellular drug levels. Rather, the expression and activity of P-gp are influenced by multiple factors that change dynamically after transplantation, including inflammatory cytokines and gut microbiota. This study longitudinally assessed P-gp activity in peripheral blood mononuclear cells from HSCT recipients. Serial measurements were taken between days 14 and 41 following transplantation. Although blood TAC trough concentrations remained within the therapeutic range (10–15&#xa0;ng/mL) throughout this period, P-gp activity increased progressively from the early (days 14–17) to the intermediate (days 38–41) post-transplantation phases. Notably, although the TAC blood concentration did not change significantly between days 14 and 17 and GVHD onset, P-gp activity was significantly elevated at GVHD onset (<i>p</i> &lt; 0.05). These findings suggest fluctuations in P-gp activity may play a role in the onset of GVHD. Early assessment of P-gp activity after HSCT may serve as a biomarker for predicting GVHD development; however, further studies are required to validate its clinical utility.</p>

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Impact of lymphocyte p-glycoprotein activity on development of graft-versus-host disease after stem cell transplantation

  • 期刊论文

  • 发表日期：

    2026年4月15日

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  • Shoji Nakamura,
  • Soichiro Tajima,
  • Takeshi Hirota,
  • Koji Kato,
  • Koichi Akashi,
  • Mayako Uchida

摘要

Tacrolimus (TAC) is a pivotal immunosuppressant used to prevent graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). However, because lymphocytes express P-glycoprotein (P-gp), which actively effluxes TAC, blood TAC concentrations do not necessarily reflect intracellular drug levels. Rather, the expression and activity of P-gp are influenced by multiple factors that change dynamically after transplantation, including inflammatory cytokines and gut microbiota. This study longitudinally assessed P-gp activity in peripheral blood mononuclear cells from HSCT recipients. Serial measurements were taken between days 14 and 41 following transplantation. Although blood TAC trough concentrations remained within the therapeutic range (10–15 ng/mL) throughout this period, P-gp activity increased progressively from the early (days 14–17) to the intermediate (days 38–41) post-transplantation phases. Notably, although the TAC blood concentration did not change significantly between days 14 and 17 and GVHD onset, P-gp activity was significantly elevated at GVHD onset (p < 0.05). These findings suggest fluctuations in P-gp activity may play a role in the onset of GVHD. Early assessment of P-gp activity after HSCT may serve as a biomarker for predicting GVHD development; however, further studies are required to validate its clinical utility.