Interferon-α in systemic lupus erythematosus

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Abstract
To describe the lines of evidence supporting a significant role for interferon-alpha (IFNalpha) in the pathogenesis of systemic lupus erythematosus (SLE) and to propose potential mechanisms by which IFNalpha contributes to the autoimmunity and immune dysfunction of SLE. Long-standing data indicating elevated levels of IFNalpha in the circulation of patients with SLE have recently been supplemented by reports from clinical practice, gene expression data, analysis of patient cells studied ex vivo, and studies of mechanisms of induction of IFNalpha production to provide complementary data strongly supporting a pathogenic role for IFNalpha in SLE. Recombinant IFNalpha, when administered as a therapy to patients with malignancy or hepatitis infection, can induce SLE. IFNalpha-regulated genes are highly expressed in SLE peripheral blood cells compared with cells from control subjects. Functional alterations of SLE mononuclear cells have been attributed to effects of IFNalpha. In addition, immune complexes bearing lupus autoantibodies and RNA or DNA have been shown to induce IFNalpha production. Finally, progress in understanding the role of Toll-like receptors (TLR) in the activation of the innate immune response has suggested potential mechanisms by which adjuvant-like factors act through TLR to induce IFNalpha as well as effective processing of self-antigens, resulting in activation of an adaptive immune response directed against self, as well as cytokine-mediated immune dysfunction. Substantial evidence supports a significant role for IFNalpha in the pathogenesis of lupus. The IFNalpha pathway represents a promising target for therapeutic intervention in patients with SLE.

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