Correlation between T cell subsets and acute graft rejection in tacrolimus-based therapy kidney transplant patients

[Speaker] Suthida Boonsom:1
[Co-author] Suda Vannaprasaht:1, Wichittra Tassaneeyakul:1, Surasakdi Wongratanacheewin:2, Cholatip Pongskul:3, Sirirat Anutrakulchai:3, Chitranon Chan-On:3
1:Department of Pharmacology, Khon Kaen University, Thailand, 2:Department of Microbiology, Khon Kaen University, Thailand, 3:Department of Medicine, Khon Kaen University, Thailand

Tacrolimus (TAC) affected T cells function lead to reduce immune response for preventing graft rejection in kidney transplant patients. TAC has a narrow therapeutic range. Therefore, TAC trough concentration were used for individualization of TAC dose to maintain drug efficacy and minimize drug overexposure. Recent data showed poor correlation between TAC trough blood concentration and clinical response and they found the correlation between acute rejection episodes and expression of T cell regulated gene in early post transplantation. Therefore, pharmacodynamics assay for TAC would be a new step forward for prospective follow-up of kidney transplant patients. This study aimed to investigate the correlation between T cell subsets and acute graft rejection from tacrolimus-based therapy kidney transplant patients.
Twenty-five tacrolimus-based therapy kidney transplant patients were observed up to 6 months. Whole blood samples were collected at trough level (C0) in day 0 (before transplantation), 2 weeks, 1 month, 3 months and 6 months after transplantation. At each time point, 5 ml of each blood sample were collected for determined TAC trough blood concentration and T cell subsets analyzed by flow cytometry. Percentages of T cell subsets (cell surface marker; CD4, and intracellular markers; IL-2) were recorded at each time point and correlated to acute graft rejection episodes.
At day 0; percentages of CD4 and IL-2 of non-graft rejection patients and acute rejection patients were similar without statistical difference. TAC levels at every visits were similar in both group and were in the therapeutic ranges (4.7-9.1 µg/ml). Acute graft rejection occurred in 7 patients. These patients showed significant higher percentages of CD4 and IL-2 compared to non-graft rejection patients at the time point 1 month and 3 months (P<0.001) as showed in figure 1.
This study indicated that T cell subsets showed a positive correlation with acute graft rejection episodes in 6 months post-transplantation. Pharmacodynamics monitoring has potential to evaluate therapeutic drug monitoring of TAC and has higher sensitivity to identify acute graft rejection than only pharmacokinetics monitoring. Therefore, T cell subsets may be new markers to adjust individual TAC level in kidney transplant patients in the future.

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