Following the mass vaccinations against pandemic
influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset
narcolepsy with
cataplexy (NC) was detected in several European countries where AS03-adjuvanted
Pandemrix vaccine had been used. NC is a chronic
neurological disorder characterized by
excessive daytime sleepiness and
cataplexy. In human NC, the
hypocretin-producing neurons in the hypothalamus or the
hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g.
HLA-DQB1*0602) and environmental risk factors (e.g.
Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus
hemagglutinin is known to bind
gangliosides, which serve as host cell
virus receptors. Anti-
ganglioside antibodies have previously been linked to various
neurological disorders, like the
Guillain-Barré syndrome which may develop after
infection or vaccination. Because of these links we screened sera of NC patients and controls for
IgG anti-
ganglioside antibodies against 11 human brain
gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a
sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with
Pandemrix-associated NC, 20 with NC without
Pandemrix association, 57
Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with
Pandemrix-associated NC had more frequently (14.6%) anti-GM3
antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3
antibodies were significantly associated with
HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-
ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of
Pandemrix-associated NC and that
autoantibodies against
gangliosides were induced by
Pandemrix vaccination.