Abstract
IFN-α, which consists of multiple subtypes, exerts antiviral, antitumour and immunomodulatory activities. Besides its role as an important mediator of protective immunity, IFN-α is also involved in the pathogenesis of several autoimmune diseases, especially systemic lupus erythematosus (SLE). In this disorder, IFN-α appears to promote the maturation of dendritic cells (DCs) capable of activating T cells, and to stimulate B cell differentiation and autoantibody secretion with formation of immune complexes that trigger enhanced IFN-α production, thereby driving the autoimmune process through a vicious circle-like mechanism. Other autoimmune diseases where IFN-α has been implicated include Type 1 diabetes, thyroiditis, Sjogren’s disease and psoriasis. Therefore, targeting IFN-α may provide a therapeutic approach for SLE and the latter diseases. Accordingly, Medarex has generated human monoclonal antibodies (mAbs) that specifically neutralise several IFN-α subtypes but not IFN-β or IFN-ω. One of these mAbs was shown to inhibit the biological activity of IFN-α on peripheral blood mononuclear cells and the inducing effect of SLE plasma on DC maturation in vitro.
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