Abstracts

Rationale: Dravet syndrome (DS) is a refractory epileptic syndrome. Vaccination is the trigger of the first seizure in about 50% of cases. Fever remains a trigger of seizures during the course of the disease. Methods: We conduct ex vivo cytokine responses of peripheral-blood mononuclear cells and monocytes after vaccine stimulation in 8 patients (DS) and their controls (HC) Results: We found that vaccine responsiveness is biased toward a pro-inflammatory profile in DS with a M1 phenotype of monocytes. In vitro stimulation with the vaccine induced in both groups a marked increase, over background, in the secretion of TH1 (IL-2, IFN-γ), Th2 (IL-4, IL-13), Th17 (IL-17) T-cell derived cytokines, as well as in the pro-inflammatory (IL-1b, IL-6, TNF-α, GCSF, GMCSF, MIP-1b) cytokines/chemokines and the immuno-regulatory IL-10 cytokine. In vitro stimulation of monocytes with the vaccine induced a significant increase over spontaneous release of IL-1b, IL-6 and TNF-α in DS but of IL-10 in HC. It is worth noting that in accordance with T-cell depletion Th1, Th2 and Th17 cytokine responses were not induced by the vaccine in monocyte preparations. After subtracting spontaneous release, monocyte response to the vaccine in DS was clearly directed towards a pro-inflammatory (IL-1b, IL-6 and TNF-α) profile associated with defective counter-regulatory IL-10 response Conclusions: We provide new insight into immune mechanisms associated with DS that might guide research for the development of new immunotherapeutic agents in this epilepsy syndrome. Funding: This work was supported by INSERM, Université Paris-Diderot, Fondation de l’Avenir