The interferons (IFNs) consist of a large family of proteins classified as type I-III IFNs and originally defined by their capacity to interfere with viral replication. Subsequent studies revealed that IFNs also have many immunomodulatory effects and can act as immune adjuvant. Among the immunostimulatory effects by type I IFN are maturation and differentiation of dendritic cells, activation of T cells and enhanced antibody production by B cells. There are several observations suggesting an important role for the type I IFN system in the etiopathogenesis of SLE. Among these are the reported development of autoimmune diseases, including SLE, during treatment with IFN and a prominent increase in the expression of type I IFN regulated genes (an IFN signature) in cells from SLE patients. Recent data also show 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. 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. Trials targeting the type I IFN receptor are also under way, and preliminary data was recently reported. Other possibilities include elimination of endogenous IFN inducers and inhibition of key molecules in the type I IFN signaling pathway. The results so far show that it's possible to partially suppress the IFN signature, improve several biomarkers and reduce disease activity in a subset of SLE patients. No major safety problems have been observed so far, but complete inhibition of the type I IFN system will automatically increase the risk for severe infections.
Disclosure of Interest L. Rönnblom Grant/research support from: Astra/Zeneca
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