Systemic lupus erythematosus and Sjögren's syndrome: Edited by Andras PerlType I interferon and lupusRönnblom, Larsa; Alm, Gunnar Vb; Eloranta, Maija-Leenaa Author Information aDepartment of Medical Sciences, Section of Rheumatology, Uppsala University, Sweden bDepartment of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden Correspondence to Lars Rönnblom, Department of Medical Sciences, Uppsala University Hospital, Entrance 40, SE-751 85 Uppsala, Sweden Tel: +46 18 6115398; e-mail: [email protected] Current Opinion in Rheumatology: September 2009 - Volume 21 - Issue 5 - p 471-477 doi: 10.1097/BOR.0b013e32832e089e Buy Metrics Abstract Purpose of review Patients with lupus have signs of an ongoing production of type I interferons (IFNs) that are of importance both for the etiopathogenesis and the clinical manifestations. In this review, we summarize the latest information concerning the type I IFN system in lupus. Recent findings Activated plasmacytoid dendritic cells are responsible for the IFNα production in lupus and can be found in target organs such as glomeruli. The plasmacytoid dendritic cells are triggered by interferogenic immune complexes, and produced IFNα activates the immune system and impairs T-regulatory cell function. Autoantibodies, which can form interferogenic immune complexes, are not only present in serum of lupus patients but also in the cerebrospinal fluid of patients with neuropsychiatric manifestations. There is a strong association between risk to develop lupus and gene variants connected to the production and effects of type I IFN. Risk variants can not only cause either increased serum IFNα activity or sensitivity but also a more severe disease phenotype. Administration of monoclonal anti-IFNα antibodies to lupus patients downregulates several proinflammatory pathways and reduces disease activity. Summary Increasing evidence indicates that the activated type I IFN system in lupus is critical in the etiopathogenesis of the disease and is an important therapeutic target. © 2009 Lippincott Williams & Wilkins, Inc.