The type I interferon (IFN) system is our main defense against viral infections and can be activated by a large number of sensors of nucleic acid, triggering 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 SLE and other autoimmune diseases. Among these are the reported development of autoimmune diseases during treatment with IFN-alpha, 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 or self derived IFN inducers in SLE patients and a genetic association between autoimmune diseases and gene variants within the type I IFN signaling pathway.
The type I IFN system is closely connected to a number of cytokine and chemokine pathways, which all can contribute to both the IFN signature and the type I IFN effects. Important type I IFN effects are maturation and differentiation of dendritic cells, activation of T and B cells with enhanced antibody production and induction of increased expression of autoantigens. Consequently, type I IFNs can act as an immune adjuvant and promote an autoimmune process. Recent data have also shown that the regulation of the type I IFN system is abnormal in SLE, which all together suggests that inhibition of the type I IFN system could be beneficial in SLE and possible also other autoimmune diseases. Many different therapeutic targets exists and several studies are in progress aiming to block, or down-regulate, the activated type I IFN system in SLE. A number of studies with monoclonal anti-IFN-alpha antibodies have been reported, and a small study investigating vaccination with an interferon-alpha-kinoid against IFN-alpha has been published. Recently, a phase IIb study targeting the type I IFN receptor in moderate to severe SLE was published, reporting substantially reduced disease activity. Other therapeutic possibilities include elimination of the endogenous IFN inducers and inhibition of key molecules in the type I IFN signaling pathway. The results so far shows that it's possible to suppress the IFN signature and improve several biomarkers in SLE patients without major safety problems. The challenge for the future is to modulate the interferon system in autoimmune diseases more precisely and realize that different treatments may be appropriate in various patients.
Disclosure of Interest L. Rönnblom Grant/research support from: AstraZeneca