학술논문
Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.
Document Type
Article
Author
Dirks, Meike; Buchert, Ralph; Wirries, Ann-Katrin; Pflugrad, Henning; Grosse, Gerrit M.; Petrusch, Carlotta; Schütze, Christian; Wilke, Florian; Mamach, Martin; Hamann, Linda; Langer, Laura B. N.; Ding, Xiao-Qi; Barg-Hock, Hannelore; Klempnauer, Jürgen; Wetzel, Christian H.; Lukacevic, Mario; Janssen, Eike; Kessler, Mariella; Bengel, Frank M.; Geworski, Lilli
Source
Subject
*CALCINEURIN
*COGNITIVE ability
*IMMUNOSUPPRESSION
*TRANSLOCATOR proteins
*EMISSION-computed tomography
*
*
*
*
Language
ISSN
1619-7070
Abstract
Purpose: Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand 18F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression. Methods: PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (VT) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance. Results: In controls, VT was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean VT corrected for TSPO genotype was significantly lower in patients compared to controls, especially in patients in whom CNI dose had been reduced because of nephrotoxic side effect. Conclusion: Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity. [ABSTRACT FROM AUTHOR]