Emerging new pathways of pathogenesis and targets for treatment in systemic lupus erythematosus and Sjogren's syndrome

Curr Opin Rheumatol. 2009 Sep;21(5):443-7. doi: 10.1097/BOR.0b013e32832efe6b.

Abstract

Purpose of review: Systemic lupus erythematosus (SLE) and Sjogren's syndrome are chronic inflammatory diseases characterized by the dysfunction of T cells, B cells, and dendritic cells and the production of antinuclear autoantibodies. Here, we evaluate newly discovered molecular and cellular targets for the treatment of SLE and Sjogren's syndrome.

Recent findings: The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models. Inhibition of oxidative stress, nitric oxide production, interferon alpha, toll-like receptors 7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, and the nuclear factor kappa B pathway showed efficacy in animal models of lupus. B-cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, whereas human studies have so far failed to accomplish clinical endpoints, possibly due to inadequacies in study design.

Summary: Discovery of novel genes and signaling pathways in lupus pathogenesis offers novel biomarker-targeted approaches for treatment of SLE and Sjogren's syndrome.

Publication types

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

MeSH terms

  • Animals
  • Genome-Wide Association Study
  • Humans
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lupus Erythematosus, Systemic / therapy
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Sjogren's Syndrome / etiology*
  • Sjogren's Syndrome / physiopathology
  • Sjogren's Syndrome / therapy