Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

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 F-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 (V) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance.

RESULTS

In controls, V was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean V 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.