Page 62 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

Chapter 4
Abstract
Introduction: Even though indirect evidence points strongly to a T cell mediated autoimmune response, the exact key immune cell populations in this response remain elusive. We aimed to identify narcolepsy type 1-specific immune cell populations using mass cytometry, a high- dimensional single-cell analysis technique that permits an in-depth examination of immune cell subtypes together with algorithm-guided analysis approaches.
Methods: Immune cell composition in the peripheral blood of 16 narcolepsy type 1 patients with recent disease onset was compared to 8 HLA-DQ6 (DQA1*01:02/DQB1*06:02)-matched healthy controls and 10 narcolepsy type 1 patients longer after disease onset by using mass cytometry.
Results: Populations of memory CD4+ and CD8+ T cells and regulatory CD4+ T cells indicative of an activated phenotype are more frequently found in the peripheral blood of narcolepsy type 1 patients than in healthy HLA-DQB1*06:02-matched controls. Additionally, differences in immune cell composition between narcolepsy type 1 patients with recent disease onset and those longer after disease onset are limited.
Conclusion: These findings point towards multifaceted immune activation in narcolepsy type 1 patients. Performing functional experiments on the immune populations discovered in this study could serve as a starting point for identifying the immune mechanisms driving the autoimmune response leading to the destruction of hypocretin- producing neurons.
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