Narcolepsy is a chronic neurological condition characterized by excessive daytime sleepiness. It causes are unknown. It is suggested that deficiency or inhibition of endogenous brain peptide called hypocretin (orexin) and produced by hypothalamus could recapitulate narcolepsy's symptoms.
New study in Science Translational Medicine suggested that immune cross-reactivity between Flu vaccine component and brain's hypocretin receptor could have caused autoantibody mediated narcolepsy following 2009 Flu H1N1.
First, the authors showed that nucleoprotein (NP) from flu vaccine Pandemrix (that caused narcolepsy) and NP from flu vaccine Focetria (that did not cause narcolepsy) have sequence similarity to human hypocretin receptor. These two NPs differed in only 1 amino acid from each other (isoleucin vs. methionine).
Next, the authors showed that serum samples from Pandermrix cohort, but not from Focetria cohort, reacted with human hypocretin receptor in a sensitive cell-based assay (note high reactivity in healthy Finish group).
Importantly, the authors showed that this immune reactivity of Pandemprix vaccinated serum samples to human hypocretin receptor could be inhibited by short Flu NP peptides (both from Pandemprix and Focetria) and or by hypocretin receptor (positive control). It suggested that at the antibody level, there is no difference between NP from Pandemrix or Focetria. The authors could not analyze T cell part.
In summary, the authors suggested the following hypothesis: high level of NP protein in Pandemrix flu vaccine (compared to Focetria) could have induced robust anti-NP antibody titre that later "somehow" have managed to cross human brain blood barrier (BBB) and caused autoimmune narcolepsy is HLA susceptible individuals. However, it is not clear how autoantibody could have got access to hypothalamic cells expressing hypocretin receptors.
Vaccine are important for human health. However, human HLA diversity and natural mimicry at the protein and peptide level could produce autoimmunity in certain individuals.