Low Production of Reactive Oxygen Species Drives Systemic Lupus Erythematosus

Trends Mol Med. 2019 Oct;25(10):826-835. doi: 10.1016/j.molmed.2019.06.001. Epub 2019 Jul 11.

Abstract

Systemic lupus erythematosus (SLE) is a common autoimmune disease. Recent findings have shown that a major single nucleotide variant predisposing to SLE is associated with low production of reactive oxygen species (ROS). A variant amino acid in a frequent NCF1 allele causing deficient ROS production leads to an exaggerated type I interferon (IFN) response, earlier disease onset, and higher susceptibility to SLE. It is the so far strongest identified single nucleotide variant, with an odds ratio (OR) of >3 and an allele frequency of >10%. Its functional role is in sharp contrast to the earlier belief that excessive ROS production is exclusively pathogenic rather than protective. It opens new possibilities to understand the pathogenesis of SLE and to develop novel diagnostics and treatment strategies.

Keywords: NADPH oxidase; interferon; neutrophil cytosolic factor 1; reactive oxygen species; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / metabolism*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Reactive Oxygen Species / metabolism*

Substances

  • Interferon Type I
  • Reactive Oxygen Species
  • NADPH Oxidases
  • neutrophil cytosolic factor 1