The Intracellular Tacrolimus Concentration in CD3+ T Lymphocytes and CD14+ Monocytes and Its Association with Kidney Transplant Rejection
Erasmus MC, Rotterdam, Netherlands
Meeting: 2022 American Transplant Congress
Abstract number: 1277
Keywords: CD3, Kidney transplantation, Rejection, T cells
Topic: Basic Science » Basic Science » 12 - Immunosuppression & Tolerance: Preclinical & Translational Studies
Session Information
Session Name: Immunosuppression & Tolerance: Preclinical & Translational Studies
Session Type: Poster Abstract
Date: Monday, June 6, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: The intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) (TAC[PBMC]) was proposed to better represent active concentration than pre-dose whole blood concentration (C0). However, in previous studies, the TAC[PBMC] did not correlate well with acute rejection. Since tacrolimus acts within T lymphocytes and other white blood cells such as monocytes, we investigated the association between the tacrolimus concentration in CD3+ T lymphocytes and CD14+ monocytes, and acute rejection after kidney transplantation.
*Methods: In this case-control study, blood samples of 37 kidney transplant recipients who underwent a for-cause biopsy were studied. Sixteen out of 37 had a biopsy-proven acute rejection (rejection group) and 21 patients had no rejection (control group). PBMCs were collected from both cryopreserved samples (retrospectively) and freshly obtained samples (prospectively). T lymphocytes and monocytes were isolated from PBMCs and their intracellular tacrolimus concentration was measured by liquid chromatography-tandem mass spectrometry.
*Results: The correlation between the tacrolimus whole blood C0 and intracellular concentrations was poor, with a correlation coefficient of r=0.33 for PBMCs, r=0.54 for T lymphocytes, and r=0.67 for monocytes. Remarkably, TAC[CD3] was significantly lower than TAC[CD14]:13.3(9.9-19.1) vs 72.8(57.3-101.7) pg/million cells (pgm);p<0.001). Patients with rejection had a comparable whole blood C0 to those without rejection (mean 9.8±2.9 vs 8.8±3.3 ng/mL;p=0.32). Also, no difference was found between the rejection group and control group regarding the TAC[PBMC] (36.0(22.8-48.5) vs 34.0(32.0-45.5) pgm;p=0.82), TAC[CD3] (13.1(9.9-15.7) vs 11.4(8.3-13.3) pgm;p=0.19), and TAC[CD14] (74.8(58.6-105.1) vs 62.3(51.0-78.8) pgm; p=0.19). However, PBMCs that were freshly isolated showed significantly higher TAC[PBMC] compared with PBMCs from cryopreserved samples (91.5(60.5-113.75) vs 34.5(28.1-47.0) pgm;p<0.001). Subgroup analysis of the intracellular tacrolimus concentration from freshly isolated cells again did not show difference between the rejectors and non-rejectors.
*Conclusions: The correlation between whole blood and intracellular tacrolimus concentrations is poor. No difference in TAC[CD3] nor TAC[CD14] concentrations between patients with and without acute rejection could be demonstrated. However, further optimization of the cell isolation process is required because a difference in TAC[PBMC] between fresh and cryopreserved cells was demonstrated.
To cite this abstract in AMA style:
Udomkarnjananun S, Baan C, Winter Bde, Hesselink D. The Intracellular Tacrolimus Concentration in CD3+ T Lymphocytes and CD14+ Monocytes and Its Association with Kidney Transplant Rejection [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/the-intracellular-tacrolimus-concentration-in-cd3-t-lymphocytes-and-cd14-monocytes-and-its-association-with-kidney-transplant-rejection/. Accessed December 13, 2024.« Back to 2022 American Transplant Congress