Elevated expression of EBV and TLRs in the brain is associated with Rasmussen’s encephalitis
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Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus (EBV) antigens as well as of Toll-like receptor 3 (TLR3), TLR9, and downstream adapter TIR-domain-containing adapter-inducing interferon-β (TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry (IHC). In the RE group, EBV antigens were detected in 53% of individuals at various expression levels. In contrast, there was no detectable EBV antigen expression in control brain tissues. Moreover, we found marked increases in the expression of TLR3, TLR9, and TRIF in the brain tissues of RE patients compared with levels in the control group. Furthermore, among RE cases, EBV expression and high TLR3 expression were associated with more severe brain atrophy. Our results suggest that the elevated expression of EBV and TLRs may be involved in RE occurrence through the activation of downstream molecules.
KeywordsRasmussen’s encephalitis (RE) Epstein-Barr virus (EBV) Toll-Like receptor (TLR) TIR-domain-containing adapter-inducing interferon-β (TRIF) epilepsy
This work was supported by the following funds: the National Natural Science Foundation of China (81471957, 81571275, 81671971, and 81701992), the Beijing Municipal Natural Science Foundation (7144217), and the Scientific Research Common Program of Beijing Municipal Commission of Education (KM201610025001).
JA, GML and YSW conceived and designed the experiments. XW and DL performed the experiments and analyzed the data. PGW, YGG, TFL and DYF contributed reagents/materials/analysis tools. XW and DL wrote the manuscript and prepared the figures and/or tables. JA and GML revised the manuscript, organized the collaboration and directed the project. All authors read and approved the final manuscript.
Compliance with Ethics Guidelines
The authors declare that they have no conflict of interest. This study was approved by the Ethics Committee of Sanbo Brain Hospital, Capital Medical University (2013 061801), and written informed consent was obtained from all participants or their guardians prior to the study.
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