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

Abstract

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-α and type I IFN-α receptor (IFNAR), as well as active immunization against IFN-α. This review describes the rationale behind these trials and the results obtained, and discusses the perspectives for further development of these drugs.

Modulation of Autoimmunity and Atherosclerosis – Common Targets and Promising Translational Approaches Against Disease –

“…80 Anti-IFNα therapy is under investigation in the "low" type I IFN subgroup of SLE patients, in whom it has been associated with clinical improvements. 81 Additional studies are needed to understand the function of type I IFNs in atherosclerosis and determine whether this class of cytokines is a therapeutic target.…”

The Plot Thickens Further for Type I Interferons in Atherosclerotic Disease

“…2 These studies prompted the field to initiate investigations into the role of type I IFNs in SLE disease progression and associated comorbidities. The IFN signature clearly associates with disease in a large proportion of the patients and is nowadays considered an attractive target for therapeutic interventions.…”

“…The IFN signature clearly associates with disease in a large proportion of the patients and is nowadays considered an attractive target for therapeutic interventions. 2 Several clinical trials targeting the type I IFN pathway have been initiated using either monoclonal antibody approaches or active immunization against IFN-α. A phase II trial using an antibody against the type I IFN receptor recently showed that it can accomplish suppression of the IFN profile and reduce disease activity in patients.…”

Current and future treatment options for cutaneous lupus erythematosus

“…Sifalimumab is a fully human immunoglobulin G1k monoclonal antibody that binds to and neutralizes a majority of the subtypes of human interferon-a. Phase I and Phase II trials in SLE patients have been performed with promising results including for cutaneous disease [82,83].…”