Type I interferon in rheumatic diseases

Nat Rev Rheumatol. 2018 Mar 21;14(4):214-228. doi: 10.1038/nrrheum.2018.31.


The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease. Inappropriate activation of the immune response via Toll-like receptors and other nucleic acid sensors also contributes to the dysregulation of the type I interferon pathway in a number of rheumatic diseases. Theoretically, differences in type I interferon activity between patients might predict response to immune-based therapies, as has been demonstrated for rheumatoid arthritis. A number of type I interferon and type I interferon pathway blocking therapies are currently in clinical trials, the results of which are promising thus far. This Review provides an overview of the many ways in which the type I interferon system affects rheumatic diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Gene Regulatory Networks
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease
  • Humans
  • Interferon Type I / metabolism*
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / genetics
  • Rheumatic Diseases / immunology
  • Signal Transduction / drug effects


  • Antirheumatic Agents
  • Interferon Type I