HLA-DRB1*14 and DQB1*05 are associated with Japanese anti-MuSK antibody-positive myasthenia gravis patients

J Neurol Sci. 2016 Apr 15:363:116-8. doi: 10.1016/j.jns.2016.02.031. Epub 2016 Feb 16.

Abstract

Background: Myasthenia gravis (MG) is an autoimmune disorder presumed to be associated with genetic susceptibility. This study aims to determine whether HLA is associated with MG in Japanese patients.

Methods: We included 58 MG patients with anti-acetylcholine receptor antibody (AChR+MG) and 14 MG patients with muscle-specific receptor tyrosine kinase (MuSK+MG) and determined HLA-A, B, DRB1 and -DQB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide and primers. AChR+MG was classified into the three subgroups: early-onset MG (EOMG; n=11), late-onset MG (LOMG; n=20), and thymoma-associated MG (n=27). Healthy volunteers (n=100) served as controls.

Results: A significant positive association was observed between MuSK+MG with the DRB1*14 [57.1%, MuSK+MG vs. 18.0%, healthy controls (HC); odds ratio (OR): 6.1] and DQB1*05 [78.6%, MuSK+MG vs. 30.0%, HC; odds ratio (OR): 8.5]. We found a negative association between LOMG and DQB1*04 [5.0%, LOMG vs. 37.0%, HC; OR: 0.09]. There was no association between other MG subgroups and HLA alleles.

Conclusion: HLA-DRB1*14 and DQB1*05 were associated with MuSK+MG, therefore these alleles may play important roles in developing MuSK+MG across the races.

Keywords: Anti-acetylcholine receptor; HLA-DQB1*05; HLA-DRB1*14; Human leukocyte antigen; Muscle-specific receptor tyrosine kinase; Myasthenia gravis.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics*
  • Autoantibodies / genetics
  • Female
  • Genetic Association Studies / methods
  • HLA-DQ beta-Chains / genetics*
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis / diagnosis
  • Myasthenia Gravis / epidemiology
  • Myasthenia Gravis / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptors, Cholinergic / genetics*
  • Retrospective Studies
  • Young Adult

Substances

  • Autoantibodies
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains
  • Receptors, Cholinergic
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases