Background

Infectious complications under immunosuppressive therapy are inevitable problems. Viral infection (include reactivation) occurs at a certain frequency even if immunosuppressive agents are totally adjusted by Pharmacokinetic Study. We focused our attention on CD8 T cell directly related to anti-viral response. In this study, PD analysis was performed on CD4 and CD8 T cells and the relevance to viral infection was examined.

Methods

PD analysis was conducted by CFSE-based T cell proliferation assay after separation of CD4 and CD8 T cells. The 50% inhibitory concentration (IC50) and the percentage of T cell proliferation values at the lower plateau (Bottom) were considered as a criterion of sensitivity to calcineurin inhibitor. Cut off levels of Bottom was 25%.

(1) Retrospective Study

Bottom and IC50 were calculated from the sigmoid curve in 9 kidney transplant recipients with viral infection and 10 without infection, which were retrospectively compared with clinical findings.

(2) Prospective Study

PD analysis-based immunosuppressive therapy was performed in 12 patients. In patients with low Bottom (=high sensitivity to CNI), CNI dose was reduced from the early postoperative day. Viral infection was examined up to 4 months after transplantation. For patients with high Bottom , the standard immunosuppressive regimen was used.

Results

(1) Analysis of CD4 T cells showed no significant trends in Bottom and IC 50 for viral infection. Regarding CD8 T cells, viral infection was significantly related to a low Bottom of TAC. (P=0.013)

(2) High sensitivity to both CSA and TAC was observed in 2 patients. CNI was reduced to once a day from day 10. Two patients showed high sensitivity to either CSA or TAC. One patient reduced the CNI dose on day 10, while the other was treated with a lower sensitivity drug at a standard dose. The remaining 8 patients with low sensitivity were given CNI at a standard dose. As a result of PD analysis based immunosuppression, the prevalence of viral infection was reduced (0/12, 0%), compared with conventional treatment (23/105, 21%).

Conclusions

Immunosuppressive therapy based on PD analysis targeting CD8 T cells was considered effective for preventing post-transplant viral infection. PD analysis can be used to improve the incompleteness of PK study, leading to implement of individualized immunosuppression.

CITATION INFORMATION: Matsuoka Y., Iwasaki K., Miwa Y., Horimi K., Uchida K., Kobayashi T. Once Daily CNI Administration Based on Pharmacodynamic Analysis for Preventing Viral Infection Am J Transplant. 2017;17 (suppl 3).

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