title: Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy.
abstract: BACKGROUND
  Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) with statins may trigger idiopathic inflammatory myositis (IIM) or immune-mediated necrotizing myopathy (IMNM). Anti-HMGCR antibodies have been detected in patients with IIM/IMNM. We aimed to determine the associations of anti-HMGCR in IIM/IMNM.
  
  
  METHODS
  Anti-HMGCR antibodies were detected by ELISA in sera from patients with IIM/IMNM.
  
  
  RESULTS
  Anti-HMGCR antibodies were detected in 19 of 207 patients with IIM/IMNM, and there was a trend toward an association with male gender (P = 0.079). Anti-HMGCR antibodies were associated strongly with statin exposure (OR = 39, P = 0.0001) and HLA-DRB1*11 (OR = 50, P < 0.0001). The highest risk for development of anti-HMGCR antibodies was among HLA-DR11 carriers exposed to statins. Univariate analysis showed a strong association of anti-HMGCR antibodies with diabetes mellitus (P = 0.008), which was not confirmed by multiple regression. Among anti-HMGCR(+) patients there was a trend toward increased malignancy (P = 0.15).
  
  
  CONCLUSIONS
  Anti-HMGCR antibodies are seen in all subtypes of IIM and IMNM and are associated strongly with statin use and HLA-DR11. Muscle Nerve 52: 196-203, 2015.
authors.affiliation: Rheumatology Department, Royal Adelaide Hospital, North Tce, Adelaide, South Australia SA, 5000, Australia.|Discipline of Medicine, Adelaide University, Adelaide, South Australia, Australia.
authors.forename: Vidya
authors.initials: V
authors.lastname: Limaye
authors.affiliation: PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Bundell
authors.affiliation: PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.|Clinical Immunology, Sir Charles Gairdner Hospital.
authors.forename: Peter
authors.initials: P
authors.lastname: Hollingsworth
authors.affiliation: PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.
authors.forename: Arada
authors.initials: A
authors.lastname: Rojana-Udomsart
authors.affiliation: West Australian Neuroscience Research Institute, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Mastaglia
authors.affiliation: Discipline of Medicine, Adelaide University, Adelaide, South Australia, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Blumbergs
authors.affiliation: Rheumatology Department, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
authors.forename: Sue
authors.initials: S
authors.lastname: Lester
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D009220:Myositis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D009336:Necrosis; D012042:Registries
chemical_list: D001323:Autoantibodies; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: HMG-CoA reductase; antibodies; immune-mediated necrotizing myopathy; muscle biopsy; myositis; statins