Type I interferon blockade in systemic lupus erythematosus: where do we stand?

SLE is an autoimmune condition characterized by loss of tolerance to chromatin constituents and the production of ANAs. The majority of SLE patients display spontaneous expression of type I IFN-induced genes in circulating mononuclear cells and peripheral tissues, and type I IFNs play a role in the pathogenesis of the disease via the sustained activation of autoreactive T and B cells necessary for the production of pathogenic autoantibodies. Several IFN-blocking strategies are currently being evaluated in clinical trials: monoclonal antibodies directed against IFN-alpha and type I IFN-alpha receptor (IFNAR), as well as active immunization against IFN-alpha. This review describes the rationale behind these trials and the results obtained, and discusses the perspectives for further development of these drugs.