Antibodies against hypocretin receptor 2 are rare in narcolepsy.

STUDY OBJECTIVES: Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay.

METHODS: Sera from 50 narcolepsy type 1 (NT1) and 11 with type 2 (NT2), 22 patients with other sleep disorders, 15 healthy controls and 93 disease controls were studied. CSFs from 3 narcoleptic patients were also subsequently included. Human embryonic kidney cells were transiently transfected with human HCRTR2, incubated with patients' sera for 1 hour at 1:20 dilution and then fixed. Binding of antibodies was detected by fluorescently-labelled secondary antibodies to human IgG and the different IgG subclasses. A non-linear visual scoring system was used from 0 to 4; samples scoring ≥ 1 were considered positive.

RESULTS: Only 3/61 patients (5%) showed a score ≥ 1, one with IgG1- and two with IgG3-antibodies, but titers were low (1:40 - 1:100). CSFs from these patients were negative. The three positive patients included one NT1 case with associated psychotic features, one NT2 patient and a NT1 patient with normal hypocretin CSF levels.

CONCLUSIONS: Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3/61 patients with narcolepsy, although only one presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination.