PMID- 32743535
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2589-9090 (Electronic)
IS  - 2589-9090 (Linking)
VI  - 3
DP  - 2020
TI  - No evidence of autoimmunity to human OX(1) or OX(2) orexin receptors in 
      Pandemrix-vaccinated narcoleptic children.
PG  - 100055
LID - 10.1016/j.jtauto.2020.100055 [doi]
LID - 100055
AB  - 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(2) 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(1) or OX(2) receptors. The analysis was based on the 
      presence or absence of autoantibody responses against analyzed proteins. Entire 
      OX(1) and OX(2) 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(2). 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.
CI  - (c) 2020 The Authors.
FAU - Melen, Krister
AU  - Melen K
AD  - Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, 
      Finland.
AD  - Expert Microbiology Unit, Finnish Institute for Health and Welfare, 
      Mannerheimintie 166, 00300, Helsinki, Finland.
FAU - Jalkanen, Pinja
AU  - Jalkanen P
AD  - Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, 
      Finland.
FAU - Kukkonen, Jyrki P
AU  - Kukkonen JP
AD  - Department of Physiology and Department of Pharmacology, Institute of 
      Biomedicine, Faculty of Medicine and Biochemistry and Cell Biology, Department of 
      Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, 
      Helsinki, Finland.
FAU - Partinen, Markku
AU  - Partinen M
AD  - Helsinki Sleep Clinic, Vitalmed Research Centre Helsinki and Medicum, Faculty of 
      Medicine, University of Helsinki, Finland.
FAU - Nohynek, Hanna
AU  - Nohynek H
AD  - Infectious Disease Control and Vaccination Unit, Finnish Institute for Health and 
      Welfare, Helsinki, Finland.
FAU - Vuorela, Arja
AU  - Vuorela A
AD  - Reseach Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki.
FAU - Vaarala, Outi
AU  - Vaarala O
AD  - Reseach Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki.
FAU - Freitag, Tobias L
AU  - Freitag TL
AD  - Department of Bacteriology and Immunology and Translational Immunology Research 
      Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
FAU - Meri, Seppo
AU  - Meri S
AD  - Department of Bacteriology and Immunology and Translational Immunology Research 
      Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
FAU - Julkunen, Ilkka
AU  - Julkunen I
AD  - Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, 
      Finland.
AD  - Turku University Hospital, Clinical Microbiology, Kiinamyllynkatu 10, 20520, 
      Turku, Finland.
LA  - eng
PT  - Journal Article
DEP - 20200501
PL  - Netherlands
TA  - J Transl Autoimmun
JT  - Journal of translational autoimmunity
JID - 101759413
PMC - PMC7388359
OTO - NOTNLM
OT  - Autoimmunity
OT  - Influenza A virus nucleoprotein
OT  - Narcolepsy
OT  - OX1
OT  - OX2
OT  - Pandemrix vaccination
COIS- The authors declare that they have no competing interests.
EDAT- 2020/08/04 06:00
MHDA- 2020/08/04 06:01
PMCR- 2020/05/01
CRDT- 2020/08/04 06:00
PHST- 2019/08/12 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/04/23 00:00 [accepted]
PHST- 2020/08/04 06:00 [entrez]
PHST- 2020/08/04 06:00 [pubmed]
PHST- 2020/08/04 06:01 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - S2589-9090(20)30022-8 [pii]
AID - 100055 [pii]
AID - 10.1016/j.jtauto.2020.100055 [doi]
PST - epublish
SO  - J Transl Autoimmun. 2020 May 1;3:100055. doi: 10.1016/j.jtauto.2020.100055. 
      eCollection 2020.