Potential role of IFNα in adult lupus

Systemic lupus erythematosus, or lupus, is one of the most intriguing diseases due to its diverse clinical picture, variable course and in the single patient also its unpredictable outcome. The etiopathogenesis of lupus has been studied intensively for many years and the disease has long been regarded as the prototype autoimmune disease. The reason for this is that a large number of different autoantibodies are produced in lupus patients and that most, if not all, cells in the immune system seem to be involved in the disease process.The most prominent feature in lupus is an immune response to nucleic acid and associated proteins, which results in autoantibody production, immune complex (IC) formation and organ inflammation. In addition, most lupus patients display several signs of an increased IFNα production, which during the past years has attracted much interest regarding the possible role of this cytokine in the disease process. This interest has been further inspired by the observation that IFNα administration to individuals without any autoimmune condition can trigger the production of antinuclear autoantibodies, and occasionally also a lupus syndrome.In the present review, the possible reason(s) behind the ongoing IFNα production in lupus will be reviewed, as well as the role of IFNα in the etiopathogenesis and the clinical manifestations of the disease. The potential application in clinical practice of our present knowledge of the type I interferon system in lupus will also be discussed.The first described cytokine abnormality in lupus patients was an increased serum level of interferon [1], which subsequently was characterized as IFNα [2]. Early studies also demonstrated that lupus patients have increased levels of IFNα-induced proteins, such as 2',5'-adenylate synthetase [3] and MxA [4]. The latter report showed that >90% of lupus patients displayed increased expression of MxA, even if measurable serum IFNα levels could not be detected. Further studies sho