Page 116 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

Chapter 1 describes a NT1 case in which an enteroviral infection may constitute the environmental trigger for the hypocretin-1 deficiency that develops. This has not been described before and highlights the possibility that a variety of infections may trigger the immune system to elicit an autoimmune response targeting the hypocretin-producing neurons. Thereby, this case report stresses the importance of future research focusing on the question how a variety of environmental triggers can lead to a similar outcome: the destruction of hypocretin-producing neurons.
• The short interval between hypocretin-1 measurement and symptom onset in this case suggests that the decrease in hypocretin-1 concentration from normal to undetectable levels may be a process lasting only a few weeks or even less
• Enteroviral infection is a new potential environmental trigger for the autoimmune response leading to NT1
In Chapter 2, we describe HLA-DQB1 associations in a cohort of NT1 patients who developed symptoms before or after the H1N1 influenza pandemic. With this approach, we address the postulation of Scandinavian researchers that post-H1N1 NT1 is a separate disease entity. Over the last few years, many studies (Juvodden et al., 2019b, Nordstrand et al., 2019a, Nordstrand et al., 2018, Bomfim et al., 2017, Juvodden et al., 2018, Sarkanen et al., 2016), particularly in Scandinavia, have focused on post-H1N1 only, thereby excluding so called sporadic NT1 patients. We argue, based on the fact that HLA-DQB1 associations have not changed since the H1N1 influenza pandemic, that there is no convincing evidence to justify a distinction between post-H1N1 and sporadic NT1.
• No differences were found in HLA-associations in pre- vs post- H1N1 NT1 patients
• Positive association of pre- and post-H1N1 NT1 with HLA-DQ7 was confirmed
• Negative associations of pre- and post-H1N1 NT1 with HLA- DQ2, -DQB1*05:01, -*06:03 were confirmed
• These results argue against sporadic and post-H1N1 NT1 being separate entities
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