The importance of the type I interferon system in autoimmunity

The type I interferon (IFN) system is our main defense against viral infections and consists of a large number of sensors of nucleic acid that can trigger the production of more than 15 different proteins with antiviral and immunostimulatory capacity. There are several observations suggesting an important role for this system in the etiopathogenesis of systemic lupus erythematosus (SLE) and other auto immune diseases. Among these are the development of autoimmune diseases during IFN-alpha treatment, a prominent increase in the expression of type I IFN regulated genes (an IFN signature) in a number of rheumatic diseases, the existence of endogenous IFN inducers in SLE patients and a genetic association between autoimmune diseases and gene variants within the type I IFN signalling pathway. Collectively, these observations suggests that inhibition of the type I IFN system could be beneficial in SLE and possible also,,other autoimmune diseases. Many different therapeutic targets exist and several studies are in progress aiming to block or down-regulate the activated type I IFN system. A number of studies with monoclonal anti-IFN-alpha antibodies in SLE patients have been reported, and a small study investigating vaccination with an interferon-alpha-kinoid against IFN-alpha has been published. Trials targeting the type I IFN receptor are under way, and other possibilities include elimination of the endogenous IFN inducers and inhibition of key molecules in the type I IFN signalling pathway. Results so far show that it is possible to partially suppress the IFN signature, improve several biomarkers and ameliorate clinical manifestations by some of these new treatment strategies.