rcolepsy. Our findings here do not provide a mechanistic link between the immune response to NP and narcolepsy, however. Given a role of DQB106:02 allele in the presentation of antigenic epitopes to CD4 T-cells, it is urgent that NP derived DQB106:02 dependent epitopes are screened. Because of limited sample availability from children, the protein composition of Pandemrix and Arepanrix had to be determined before proceeding to T-cell epitope screens. This proposed screen could reveal the environmental driving antigen of narcolepsy related autoimmunity. If Pandemrix PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19682730 contained an antigen-specific trigger of narcolepsy, as suggested by the epidemiological and immunological evidence discussed above, the increased risk of narcolepsy in the vaccinated individuals may be seen years after vaccination. On the other hand, it also explains why PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1968231 in some individuals such a rapid development of narcolepsy was seen after Pandemrix vaccination; in some cases the underlying narcolepsy related autoimmunity was specifically reactivated by Pandemrix. The association of H1N1 virus SCH 58261 infection with increased incidence of narcolepsy has been reported in China. Our serological studies performed in the same series of patients as studied here do not provide evidence for the role of H1N1 infection as a contributing factor for the increase of narcolepsy in children and adolescents observed in 20092010. The ecological studies in South Korea do not either support the association of H1N1 infection and narcolepsy. It is of interest that H1N1 vaccines contain NP, which originates from H1N1 Puerto Rico 1934 strain and not from the pandemic H1N1 influenza strain. A role of H1N1 virus derived HA in narcolepsy was suggested based on the molecular mimicry of DQB106:02 binding epitopes between HA and hypocretin peptides, but this report was later retracted due to the lack of reproducibility of the findings. Here we show that the children with narcolepsy have enhanced antibody reactivity to recombinant HA. Increased antibody levels to H1N1 viral HA were reported also in Swedish children with narcolepsy when measured with a radio-immunoprecipitation assay using in vitro coupled transcription translation HA. However, no significant difference was seen in the antibody reactivity of the healthy children and children with narcolepsy when HA antibody titers were studied in the HI test using the H1N1 pandemic strain, the strain used in the Pandemrix vaccine. The role of HA as a trigger of narcolepsy is further challenged by the lack of the epidemiological evidence associating narcolepsy with other H1N1 vaccines containing also HA as the major immunogen. This is despite all pandemic and seasonal flu-vaccines administered after 2009 have contained immunogenic HA from H1N1 A/California/7/2009 virus, including Arepanrix, which contained the same adjuvant as Pandemrix, i.e., AS03. 19 / 23 Influenza A Vaccine Antigen and Narcolepsy Risk The market authorization holder of both Arepanrix and Pandemrix, GSK, sponsored epidemiological research on narcolepsy in association with Arepanrix for a more robust assessment of the association than the studies that had been performed in Europe for Pandemrix. In order to determine antigen equivalence of the two preparations they used HI test. Our observations here imply that the HI test is too limited in scope to reveal quantitative and qualitative differences in the myriad immunogens found in these H1N1 vaccine preparations. No prospective, pre-vaccinatio

However, the mechanisms remain largely unknown

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