Type 1
narcolepsy is caused by deficiency of hypothalamic
orexin/
hypocretin. An autoimmune basis is suspected, but no specific
antibodies, either causative or as
biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03)
vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of
narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1
narcolepsy were tested for
autoantibodies to known neuronal
antigens including the
N-methyl-D-aspartate receptor (NMDAR) and contactin-associated
protein 2 (CASPR2), both associated with
encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of
melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without
narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2
antibodies or binding to neurons; 4/13 sera bound to
orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in
orexin-deficient
narcolepsy patients compared with
orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total
IgG levels or in CASPR2 or NMDAR
antibodies three weeks following vaccination. In conclusion, there were no
narcolepsy-specific
autoantibodies identified in type 1
narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children.
Antibodies to other neuronal specific membrane targets, with their potential for directing use of
immunotherapies, are still an important goal for future research.