Mitochondrial dysfunction in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotising myopathy

Neuromuscul Disord. 2022 May;32(5):441-444. doi: 10.1016/j.nmd.2022.03.005. Epub 2022 Mar 25.

Abstract

Mitochondrial dysfunction is a plausible cause of muscle fibre damage in a number of myopathies including immune-mediated necrotising myopathy. However, histopathological evidence of mitochondrial dysfunction is not often described in immune-mediated necrotising myopathy and, when present, it is often attributed to patient age. The purpose of this study was to describe features of mitochondrial dysfunction on muscle biopsy in anti-3‑hydroxy-3-methylglutaryl-CoA reductase immune-mediated necrotising myopathy and explore whether these features are age-related. In this observational case control study, a statistically significant increase in the number of muscle fibres with increased lipid content (p = 0.004) and cytochrome c oxidase-negative/succinate dehydrogenase-positive fibres (p = 0.037) in anti-3‑hydroxy-3-methylglutaryl-coenzyme immune-mediated necrotising myopathy was found compared to age-matched controls. Therefore, histopathological features of mitochondrial dysfunction are more frequent in anti-3‑hydroxy-3-methylglutaryl-coenzyme immune-mediated necrotising myopathy than aged-matched controls and therefore, may be contributing to the pathogenesis.

Keywords: HMGCR; Mitochondria; Muscle biopsy; Myositis.

MeSH terms

  • Autoantibodies
  • Autoimmune Diseases* / pathology
  • Case-Control Studies
  • Coenzymes
  • Humans
  • Hydroxymethylglutaryl CoA Reductases
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Mitochondria / pathology
  • Muscle, Skeletal / pathology
  • Muscular Diseases* / pathology
  • Myositis* / pathology
  • Necrosis / pathology

Substances

  • Autoantibodies
  • Coenzymes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases