title: HLA-DRB1*14 and DQB1*05 are associated with Japanese anti-MuSK antibody-positive myasthenia gravis patients.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Japan. Electronic address: auzawa@chiba-u.jp.
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Uzawa
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Japan; Department of Neurology, Neurology Chiba Clinic, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawaguchi
authors.affiliation: Department of Clinical Laboratory, Chiba-East National Hospital, Japan.
authors.forename: Tateo
authors.initials: T
authors.lastname: Sakamaki
authors.affiliation: Department of Neurology, Chiba-East National Hospital, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Yoshiyama
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Himuro
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Oda
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwabara
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anti-acetylcholine receptor; HLA-DQB1*05; HLA-DRB1*14; Human leukocyte antigen; Muscle-specific receptor tyrosine kinase; Myasthenia gravis