Emerging therapies for systemic lupus erythematosus--focus on targeting interferon-alpha

Clin Immunol. 2012 Jun;143(3):210-21. doi: 10.1016/j.clim.2012.03.005. Epub 2012 Apr 6.


Current therapies for systemic lupus erythematosus (SLE), a debilitating, potentially lethal, multifactorial systemic autoimmune disease, are limited to suppressing disease activity and are associated with multiple adverse effects. Recent advances in basic and translational sciences have elucidated a crucial role for the interferon-alpha (IFNα) pathway in the pathogenesis of this enigmatic disease. The so-called "type I interferon signature" has emerged as a major risk factor for disease activity of SLE. Multiple genes encoding for molecules within the type I interferon pathway have been associated with SLE in genome wide association studies. In addition, innate immune receptors are thought to be triggered by either endogenous and/or exogenous stimuli that lead to hypersecretion of IFNα. We review the multiple emerging treatment strategies targeting IFNα-related pathways. These include monoclonal antibodies against IFNα, anti-IFNα antibody-inducing vaccines, and inhibitors of Toll-like receptors. We also summarize the current status of these pharmaceutical agents in early clinical trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Interferon-alpha / antagonists & inhibitors*
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Mice
  • Toll-Like Receptors / antagonists & inhibitors
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology


  • Interferon Regulatory Factors
  • Interferon-alpha
  • Toll-Like Receptors