Systemic lupus erythematosus and the type I interferon system

Arthritis Res Ther. 2003;5(2):68-75. doi: 10.1186/ar625. Epub 2003 Jan 20.


Patients with systemic lupus erythematosus (SLE) have ongoing interferon-alpha (IFN-alpha) production and serum IFN-alpha levels are correlated with both disease activity and severity. Recent studies of patients with SLE have demonstrated the presence of endogenous IFN-alpha inducers in such individuals, consisting of small immune complexes (ICs) containing IgG and DNA. These ICs act specifically on natural IFN-alpha-producing cells (NIPCs), often termed plasmacytoid dendritic cells (PDCs). Given the fact that the NIPC/PDC has a key role in both the innate and adaptive immune response, as well as the many immunoregulatory effects of IFN-alpha, these observations might be important for the understanding of the etiopathogenesis of SLE. In this review we briefly describe the biology of the type I IFN system, with emphasis on inducers, producing cells (especially NIPCs/PDCs), IFN-alpha actions and target immune cells that might be relevant in SLE. On the basis of this information and results from studies in SLE patients, we propose a hypothesis that explains how NIPCs/PDCs become activated and have a pivotal etiopathogenic role in SLE. This hypothesis also indicates new therapeutic targets in this autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Dendritic Cells / immunology
  • Humans
  • Interferon Type I / antagonists & inhibitors
  • Interferon Type I / physiology*
  • Interferon-alpha / physiology
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / immunology*


  • Interferon Type I
  • Interferon-alpha