PMID- 23950869
OWN - NLM
STAT- MEDLINE
DCOM- 20140430
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - No serological evidence of influenza A H1N1pdm09 virus infection as a 
      contributing factor in childhood narcolepsy after Pandemrix vaccination campaign 
      in Finland.
PG  - e68402
LID - 10.1371/journal.pone.0068402 [doi]
LID - e68402
AB  - BACKGROUND: Narcolepsy cataplexy syndrome, characterised by excessive daytime 
      sleepiness and cataplexy, is strongly associated with a genetic marker, human 
      leukocyte antigen (HLA) DQB1*06:02. A sudden increase in the incidence of 
      childhood narcolepsy was observed after vaccination with AS03-adjuvanted 
      Pandemrix influenza vaccine in Finland at the beginning of 2010. Here, we 
      analysed whether the coinciding influenza A H1N1pdm pandemic contributed, 
      together with the Pandemrix vaccination, to the increased incidence of childhood 
      narcolepsy in 2010. The analysis was based on the presence or absence of antibody 
      response against non-structural protein 1 (NS1) from H1N1pdm09 virus, which was 
      not a component of Pandemrix vaccine. METHODS: Non-structural (NS) 1 proteins 
      from recombinant influenza A/Udorn/72 (H3N2) and influenza A/Finland/554/09 
      (H1N1pdm09) viruses were purified and used in Western blot analysis to determine 
      specific antibody responses in human sera. The sera were obtained from 45 
      patients who fell ill with narcolepsy after vaccination with AS03-adjuvanted 
      Pandemrix at the end of 2009, and from controls. FINDINGS: Based on quantitative 
      Western blot analysis, only two of the 45 (4.4%) Pandemrix-vaccinated narcoleptic 
      patients showed specific antibody response against the NS1 protein from the 
      H1N1pdm09 virus, indicating past infection with the H1N1pdm09 virus. Instead, 
      paired serum samples from patients, who suffered from a laboratory confirmed 
      H1N1pdm09 infection, showed high levels or diagnostic rises (96%) in H1N1pdm 
      virus NS1-specific antibodies and very high cross-reactivity to H3N2 subtype 
      influenza A virus NS1 protein. CONCLUSION: Based on our findings, it is unlikely 
      that H1N1pdm09 virus infection contributed to a sudden increase in the incidence 
      of childhood narcolepsy observed in Finland in 2010 after AS03-adjuvanted 
      Pandemrix vaccination.
FAU - Melen, Krister
AU  - Melen K
AD  - Department of Infectious Disease Surveillance and Control, National Institute for 
      Health and Welfare, Helsinki, Finland. krister.melen@thl.fi
FAU - Partinen, Markku
AU  - Partinen M
FAU - Tynell, Janne
AU  - Tynell J
FAU - Sillanpaa, Maarit
AU  - Sillanpaa M
FAU - Himanen, Sari-Leena
AU  - Himanen SL
FAU - Saarenpaa-Heikkila, Outi
AU  - Saarenpaa-Heikkila O
FAU - Hublin, Christer
AU  - Hublin C
FAU - Olsen, Paivi
AU  - Olsen P
FAU - Ilonen, Jorma
AU  - Ilonen J
FAU - Nohynek, Hanna
AU  - Nohynek H
FAU - Syrjanen, Ritva
AU  - Syrjanen R
FAU - Kilpi, Terhi
AU  - Kilpi T
FAU - Vuorela, Arja
AU  - Vuorela A
FAU - Kirjavainen, Turkka
AU  - Kirjavainen T
FAU - Vaarala, Outi
AU  - Vaarala O
FAU - Julkunen, Ilkka
AU  - Julkunen I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130808
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Influenza Vaccines)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 0 (pandemrix)
SB  - IM
MH  - Adolescent
MH  - Antibody Formation
MH  - Child
MH  - Child, Preschool
MH  - Finland/epidemiology
MH  - Humans
MH  - Influenza A Virus, H1N1 Subtype/*immunology
MH  - Influenza A Virus, H3N2 Subtype/immunology
MH  - Influenza Vaccines/*adverse effects/*therapeutic use
MH  - Influenza, Human/*complications/epidemiology/*immunology/prevention & control
MH  - Narcolepsy/*etiology
MH  - Pandemics
MH  - Serologic Tests
MH  - Viral Nonstructural Proteins/immunology
PMC - PMC3738560
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/21 06:00
MHDA- 2014/05/03 06:00
PMCR- 2013/08/08
CRDT- 2013/08/17 06:00
PHST- 2013/02/27 00:00 [received]
PHST- 2013/05/28 00:00 [accepted]
PHST- 2013/08/17 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/05/03 06:00 [medline]
PHST- 2013/08/08 00:00 [pmc-release]
AID - PONE-D-13-10440 [pii]
AID - 10.1371/journal.pone.0068402 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 8;8(8):e68402. doi: 10.1371/journal.pone.0068402. eCollection 
      2013.