tetano
Editor, Senior Moderator
J Transl Autoimmun
. 2020 May 1;3:100055.
doi: 10.1016/j.jtauto.2020.100055. eCollection 2020.
No evidence of autoimmunity to human OX [SUB]1[/SUB] or OX [SUB]2[/SUB] orexin receptors in Pandemrix-vaccinated narcoleptic children
Krister Mel?n[SUP] 1 2 [/SUP], Pinja Jalkanen[SUP] 1 [/SUP], Jyrki P Kukkonen[SUP] 3 [/SUP], Markku Partinen[SUP] 4 [/SUP], Hanna Nohynek[SUP] 5 [/SUP], Arja Vuorela[SUP] 6 [/SUP], Outi Vaarala[SUP] 6 [/SUP], Tobias L Freitag[SUP] 7 [/SUP], Seppo Meri[SUP] 7 [/SUP], Ilkka Julkunen[SUP] 1 8 [/SUP]
Affiliations
Abstract
Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX[SUB]2[/SUB] orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX[SUB]1[/SUB] or OX[SUB]2[/SUB] receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX[SUB]1[/SUB] and OX[SUB]2[/SUB] receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX[SUB]2[/SUB]. Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors.
Keywords: Autoimmunity; Influenza A virus nucleoprotein; Narcolepsy; OX1; OX2; Pandemrix vaccination.
. 2020 May 1;3:100055.
doi: 10.1016/j.jtauto.2020.100055. eCollection 2020.
No evidence of autoimmunity to human OX [SUB]1[/SUB] or OX [SUB]2[/SUB] orexin receptors in Pandemrix-vaccinated narcoleptic children
Krister Mel?n[SUP] 1 2 [/SUP], Pinja Jalkanen[SUP] 1 [/SUP], Jyrki P Kukkonen[SUP] 3 [/SUP], Markku Partinen[SUP] 4 [/SUP], Hanna Nohynek[SUP] 5 [/SUP], Arja Vuorela[SUP] 6 [/SUP], Outi Vaarala[SUP] 6 [/SUP], Tobias L Freitag[SUP] 7 [/SUP], Seppo Meri[SUP] 7 [/SUP], Ilkka Julkunen[SUP] 1 8 [/SUP]
Affiliations
- PMID: 32743535
- PMCID: PMC7388359
- DOI: 10.1016/j.jtauto.2020.100055
Abstract
Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX[SUB]2[/SUB] orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX[SUB]1[/SUB] or OX[SUB]2[/SUB] receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX[SUB]1[/SUB] and OX[SUB]2[/SUB] receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX[SUB]2[/SUB]. Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors.
Keywords: Autoimmunity; Influenza A virus nucleoprotein; Narcolepsy; OX1; OX2; Pandemrix vaccination.