Abstract
Type I interferon (IFN) is a primary pathogenic factor in systemic lupus erythematosus (SLE). Gain-of-function genetic variants in the type I IFN pathway have been associated with risk of disease. Common polygenic as well as rare monogenic influences on type I IFN have been demonstrated, supporting a complex genetic basis for high IFN in many SLE patients. Both SLE-associated autoantibodies and high type I IFN can be observed in the pre-disease state. Patients with SLE and evidence of high type I IFN have more active disease and a greater propensity to nephritis and other severe manifestations. Despite the well-established association between type I IFN and SLE, the specific triggers of type I IFN production, the mechanisms by which IFNs help perpetuate the cycle of autoreactive cells and autoantibody production are not completely clear. This review provides an updated overview of type I IFN in SLE pathogenesis, clinical manifestations, and current therapeutic strategies targeting this pathway.