[P1-27] The Analysis of Toll-like Receptor Expression and Response in Encephalitis/encephalopathy Children Presenting with Refractory Seizures
[Introduction] Defective human TLR3 signaling causes recurrent and refractory herpes simplex encephalitis/encephalopathy. Children with encephalitis/encephalopathy presenting with refractory epilepsy may have defective TLR responses.
[Methodology] Children with encephalitis/encephalopathy and frequent seizures ≧3 episodes/day over 5 days refractory to two kinds of antiepileptic drugs and status epilepticus were enrolled to evaluate TLR1-9 responses (IL-6, IL-8, IL-12p40, INF-α, INF-γ, and TNF-α) in their peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MDDCs), compared to those with febrile convulsion and non-refractory epilepsy with/without underlying encephalitis/encephalopathy.
[Results] Five enrolled patients (1 female; 2-13 years) trended to have impaired TLR responses and significantly lower in TLR3, TLR4, TLR7/8, and TLR9 responses despite normal TLR expressions and candidate genes for defective TLR3 signaling. They also had diminished naïve T and T regulatory cells, and weakened phagocytosis. There were no detectable pathogens or anti-neuronal autoantibodies in the CSF; however, adenovirus and enterovirus were in the throat cultures (n=2) as well as serologic IgM elevation of mycoplasma pneumonia (n=1) and herpes simplex virus (n=1).
[Conclusions] Children with encephalitis/encephalopathy and refractory seizures but undetectable pathogens in their CSF could have impaired TLR3, TLR4, TLR7/8, and TLR9 responses possibly relating to their weakened phagocytosis and decreased T regulatory cells.
[Methodology] Children with encephalitis/encephalopathy and frequent seizures ≧3 episodes/day over 5 days refractory to two kinds of antiepileptic drugs and status epilepticus were enrolled to evaluate TLR1-9 responses (IL-6, IL-8, IL-12p40, INF-α, INF-γ, and TNF-α) in their peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MDDCs), compared to those with febrile convulsion and non-refractory epilepsy with/without underlying encephalitis/encephalopathy.
[Results] Five enrolled patients (1 female; 2-13 years) trended to have impaired TLR responses and significantly lower in TLR3, TLR4, TLR7/8, and TLR9 responses despite normal TLR expressions and candidate genes for defective TLR3 signaling. They also had diminished naïve T and T regulatory cells, and weakened phagocytosis. There were no detectable pathogens or anti-neuronal autoantibodies in the CSF; however, adenovirus and enterovirus were in the throat cultures (n=2) as well as serologic IgM elevation of mycoplasma pneumonia (n=1) and herpes simplex virus (n=1).
[Conclusions] Children with encephalitis/encephalopathy and refractory seizures but undetectable pathogens in their CSF could have impaired TLR3, TLR4, TLR7/8, and TLR9 responses possibly relating to their weakened phagocytosis and decreased T regulatory cells.