The role of Th17 lymphocytes in drug-resistant epilepsy

Abstract

Epilepsy is a chronic neuronal disorder affecting ~65 millions people throughout the world. 1/3 of patients suffer from drug-resistant epilepsy (DRE). Objective to assess the relationship between different Th17 markers and the clinical course of epilepsy to uncover new potential immune biomarkers and therapeutic targets of interest for DRE. Approach Subjects between 19–55 years old with a focal diagnosed epilepsy were recruited at the CHUM epilepsy clinic. The profile of peripheral blood T lymphocytes from DRE patients (n=48) is compared to well-controlled epilepsy (WCE; n=30) and healthy controls (n=35). Peripheral blood mononuclear cells (PBMCs) were isolated by gradient density centrifugation before ex vivo analysis of surface markers (flow cytometry). Total CD4 T lymphocytes were magnetically isolated from PBMCs and stimulated overnight before analysis of cytokine expression or processed for RNA extraction before analysis of transcription factors expression by qRT-PCR. Results Our data suggest that antiepileptic drugs are associated with a relative ‘immunosuppression’, more pronounced in WCE. Epilepsy is associated with an altered distribution of immune cell populations with a higher CD4:CD8 ratio. A higher proportion of CD4 T lymphocytes from DRE subjects express CCR6 and CD161 compared to WCE. The proportion of CD4 T cells expressing pro-inflammatory cytokines from Th17/1 lineage (IL-17A, IL-22, IFN-γ, GM-CSF, TNFα) is higher in DRE than WCE, while anti-inflammatory cytokines (IL-4, IL-10) tend to be lower. Conclusion Our preliminary results suggest an increased frequency of pro-inflammatory Th17/1 lymphocytes and their related cytokines in DRE. Pro-inflammatory CD4 T cells could play a role in DRE.