Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset

PLoS One. 2017 Oct 16;12(10):e0186383. doi: 10.1371/journal.pone.0186383. eCollection 2017.


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.

MeSH terms

  • Adolescent
  • Age of Onset*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Genetic Loci / genetics
  • Genetic Predisposition to Disease / genetics
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Infant
  • Male
  • Myasthenia Gravis / epidemiology
  • Myasthenia Gravis / genetics*
  • Norway / epidemiology
  • Puberty*


  • HLA-DRB1 Chains
  • HLA-DRB1*04 antigen

Grant support

This work was supported by the University of Oslo. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.