Page 18 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

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Composition of the immune system in NT1
Another approach to identifying the components involved in the autoimmune response that destroys the hypocretin-producing neurons is to identify populations of immune cells that are enriched in NT1 patients compared with healthy controls. Preferably, this must be done in a way that is independent of the presumed autoantigen to focus solely on the immune cell populations that are present in NT1 patients and healthy controls. The composition of the immune system can either be tested in peripheral blood mononuclear cells or in cerebrospinal fluid. Several studies have compared the composition of the immune system in NT1 with that of healthy controls using flow cytometry in which a global T cell activation in peripheral blood of NT1 patients (Lecendreux et al., 2017, Moresco et al., 2018) and an even stronger T cell activation was seen in the cerebrospinal fluid compared with healthy controls (Moresco et al., 2018). In Chapter 4, we apply mass cytometry, a technique that is able to delineate immune cell subsets in the peripheral blood with unprecedented resolution, to assess the differences in immune cell composition between NT1 patients with recent symptom onset and HLA-DQB1*06:02-matched healthy controls.
Clinical features of NT1
NT1 is traditionally characterized by its four core symptoms: excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations. Disturbed nocturnal sleep is generally considered to be the fifth core symptom (Black et al., 2017, Bassetti et al., 2019, Kornum et al., 2017b). Although this summary of core symptoms is widespread and acceptable for many sleep specialists, it frequently does not describe the burden of the disorder for a NT1 patient very well. A better picture of the disorder can be generated by focusing on the everyday life of a NT1 patient. With the development of the disorder, frequently in adolescence or shortly after, patients experience an inability to stay awake and concentrated for longer periods of time, interfering with social interaction, education and professional life throughout the years. This is often combined with the inability to stay asleep during the night. In addition, partial expressions of (non-)REM sleep phenomena during the day, such as automatic behavior (non-REM), cataplexy, hypnagogic hallucinations and sleep paralysis (REM), further complicate effective participation in societal life. Also, comorbidities and symptoms such as mood and anxiety disorders (Lopez et al., 2017, Ruoff et al., 2017), autonomic disturbances (Plazzi et al., 2011), apathy, fatigue (Nordstrand