Page 16 - The autoimmune hypothesis of narcolepsy and its unexplored clinical features M.S. Schinkelshoek

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Figure 1. A depiction of the autoimmune hypothesis of narcolepsy, as described in the paragraph above.
Autoreactive immune cells
The hypothesis that cross-reactivity to the 2009 H1N1 influenza virus and hypocretin peptide has led to the development of NT1 in people at risk sparked the search for components of the immune system that are capable of mounting this cross-reactive immune response.
Since many autoimmune disease in the brain are mediated by autoantibodies, these seemed the most promising suspect to target hypocretin-producing neurons, leading to their destruction. However, no studies have been able to find an enrichment of autoantibodies specific for hypocretin or its precursor in NT1 (Giannoccaro et al., 2017, Luo et al., 2017, van der Heide et al., 2015a). Some studies report higher titres of autoantibodies that target antigens moderately specific for hypocretin-producing neurons or specific for peptides in the 2009 H1N1 influenza A virus in NT1 patients (Cvetkovic-Lopes et al., 2010, Lind et al., 2017, Saariaho et al., 2015, Thebault et al., 2015). Another study focusing on the human OX2 receptor reported the presence of a mimic peptide from the influenza nucleoprotein A, used in the 2009 H1N1 influenza A vaccination campaign, that shared protein residues with a fragment of the extracellular part of the OX2 receptor (Ahmed et al., 2015). Furthermore, this study demonstrates that antibodies present in NT1 patient serum cross-react with both the influenza nucleoprotein A and the extracellular part of the OX2 receptor. However, the