PMID- 29036181
OWN - NLM
STAT- MEDLINE
DCOM- 20171106
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 10
DP  - 2017
TI  - Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated 
      with prepubertal onset.
PG  - e0186383
LID - 10.1371/journal.pone.0186383 [doi]
LID - e0186383
AB  - BACKGROUND: Juvenile myasthenia gravis (MG) is a rare autoantibody mediated 
      autoimmune disorder targeting the neuromuscular endplate. The clinical hallmark 
      is muscle weakness and fatigability. Disease aetiology is complex, including both 
      genetic and environmental factors. The involvement of genes in the human 
      leukocyte antigen (HLA) is well established in adult MG. However, HLA 
      associations in European juvenile MG have not been studied. This case-control 
      study aimed to investigate and characterize genetic risk factors in prepubertal 
      and postpubertal onset juvenile MG. METHODOLOGY/PRINCIPAL FINDINGS: A population 
      based Norwegian cohort of 43 juvenile MG patients (17 with prepubertal onset, 26 
      with postpubertal onset) and 368 controls were included. Next generation 
      sequencing of five HLA loci (HLA-A, -B, -C, -DRB1 and -DQB1) was performed, and a 
      positive association was seen with HLA-B*08 (OR (95% CI) = 3.27 (2.00-5.36), Pc = 
      0.00003) and HLA-DRB1*04:04 (OR (95% CI) = 2.65 (1.57-4.24), Pc = 0.03). 
      Stratified in postpubertal and prepubertal onset, HLA-DRB1*04:04 was only 
      positively associated with the latter (P = 0.01). The HLA-B*08 allele (12.9% in 
      the controls), previously described associated with early onset adult MG, was 
      most frequently observed in postpubertal onset MG (40.4%, P = 0.0002) but also 
      increased among prepubertal onset MG (23.5%, P = 0.05). CONCLUSION: This study 
      provides novel information about HLA susceptibility alleles in Norwegian juvenile 
      MG where HLA-DRB1*04:04 was associated with prepubertal onset.
FAU - Popperud, T H
AU  - Popperud TH
AUID- ORCID: 0000-0002-1036-5949
AD  - Department of Neurology, Oslo University Hospital, Oslo, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
AD  - Unit for hereditary and inborn neuromuscular disorders, Department of Neurology, 
      Oslo University Hospital, Oslo, Norway.
FAU - Viken, M K
AU  - Viken MK
AD  - Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, 
      Norway.
FAU - Kerty, E
AU  - Kerty E
AD  - Department of Neurology, Oslo University Hospital, Oslo, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
FAU - Lie, B A
AU  - Lie BA
AD  - Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, 
      Norway.
AD  - Department of Medical Genetics, University of Oslo and Oslo University Hospital, 
      Oslo, Norway.
LA  - eng
PT  - Journal Article
DEP - 20171016
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*04 antigen)
SB  - IM
MH  - Adolescent
MH  - *Age of Onset
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Genetic Loci/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Myasthenia Gravis/epidemiology/*genetics
MH  - Norway/epidemiology
MH  - *Puberty
PMC - PMC5643110
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/10/17 06:00
MHDA- 2017/11/07 06:00
PMCR- 2017/10/16
CRDT- 2017/10/17 06:00
PHST- 2017/05/03 00:00 [received]
PHST- 2017/09/30 00:00 [accepted]
PHST- 2017/10/17 06:00 [entrez]
PHST- 2017/10/17 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2017/10/16 00:00 [pmc-release]
AID - PONE-D-17-17026 [pii]
AID - 10.1371/journal.pone.0186383 [doi]
PST - epublish
SO  - PLoS One. 2017 Oct 16;12(10):e0186383. doi: 10.1371/journal.pone.0186383. 
      eCollection 2017.