Interferon-alpha: a therapeutic target in systemic lupus erythematosus. Academic Article uri icon

Overview

abstract

  • The long history of elevated interferon (IFN)-alpha in association with disease activity in patients who have systemic lupus erythematosus (SLE) has assumed high significance in the past decade, with accumulating data strongly supporting broad activation of the type I IFN pathway in cells of patients who have lupus, and association of IFN pathway activation with significant clinical manifestations of SLE and increased disease activity based on validated measures. In addition, a convincing association of IFN pathway activation with the presence of autoantibodies specific for RNA-binding proteins has contributed to delineation of an important role for Toll-like receptor activation by RNA-containing immune complexes in amplifying innate immune system activation and IFN pathway activation. Although the primary triggers of SLE and the IFN pathway remain undefined, rapid progress in lupus genetics is helping define lupus-associated genetic variants with a functional relationship to IFN production or response in patients. Together, the explosion of data and understanding related to the IFN pathway in SLE have readied the lupus community for translation of those insights to improved patient care. Patience will be needed to allow collection of clinical data and biologic specimens across multiple clinical centers required to support testing of IFN activity, IFN-inducible gene expression and chemokine gene products as candidate biomarkers. Meanwhile, promising clinical trials are moving forward to test the safety and efficacy of monoclonal antibody inhibitors of IFN-alpha. Other therapeutic approaches to target the IFN pathway may follow close behind.

publication date

  • February 1, 2010

Research

keywords

  • Interferon-alpha
  • Lupus Erythematosus, Systemic

Identity

PubMed Central ID

  • PMC2843146

Scopus Document Identifier

  • 77349098305

Digital Object Identifier (DOI)

  • 10.1016/j.rdc.2009.12.008

PubMed ID

  • 20202598

Additional Document Info

volume

  • 36

issue

  • 1