Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy

Muscle Nerve. 2015 Aug;52(2):196-203. doi: 10.1002/mus.24541. Epub 2015 Jan 6.

Abstract

Introduction: 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.

Keywords: HMG-CoA reductase; antibodies; immune-mediated necrotizing myopathy; muscle biopsy; myositis; statins.

MeSH terms

  • Aged
  • Autoantibodies / blood*
  • Cohort Studies
  • Female
  • Genetic Association Studies* / methods
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / blood*
  • Male
  • Middle Aged
  • Muscular Diseases / blood
  • Muscular Diseases / diagnosis
  • Muscular Diseases / genetics
  • Myositis / blood*
  • Myositis / diagnosis
  • Myositis / genetics*
  • Necrosis
  • Registries

Substances

  • Autoantibodies
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases