Printed Poster | Session 2

021 – The role of Th17 lymphocytes in drug resistant epilepsy

Oumarou Ouédraogo (1) – Helène Jamann (1) – Victoria Mamane (1) – Audrey Daigneault (2) – Marie Laure Clenet (1) – Boaz Lahav (3) – A. Berubé (3) – Marck Keezer (3) – Dang Khoa Guyen (1) – Catherine Larochelle (1)
Univ. of Montréal, CR CHUM, Montreal, Canada (1) – CR CHUM, CR CHUM, Montréal, Canada (2) – CHUM, CR CHUM, Montréal, Canada (3)

Introduction: Epilepsy is a chronic central nervous system condition affecting 1 in 100 individuals around the world. One third of patients suffer from drug-resistant epilepsy (DRE). There is a need to develop biomarkers and new therapeutic targets for DRE. Recent studies suggest a link between neuroinflammation and DRE. Indeed, pro-inflammatory Th17 lymphocytes would be more frequent in intractable childhood epilepsy and could correlate with seizure frequency in adults, although this is still controversial. We hypothesized that CD4 T cells could play a role in drug resistant epilepsy. Objectives: To assess the relationship between different Th17/1 lymphocytes markers and the clinical course of epilepsy to uncover new potential immune biomarkers and therapeutic targets of interest for drug resistant epilepsy. Approach: Subjects between 20-59 years old with a diagnosis of focal epilepsy were recruited at the CHUM epilepsy clinic. The profile of peripheral blood T lymphocytes from DRE patients (n=55) is compared to well-controlled epilepsy (WCE; n=42) and healthy controls (n=41). Peripheral blood mononuclear cells (PBMCs) are isolated by gradient density centrifugation before ex vivo analysis of surface markers (flow cytometry). Total CD4 T lymphocytes are 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. Serum cytokines analysis is performed by ELISA. 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 perpetuating DRE.