In Aicardi-Goutières syndrome (AGS), as in systemic lupus erythematosus (SLE) and Sjögren's syndrome, an increased level of interferon alpha (IFN-alpha) is involved in the pathogenesis of the disease. In SLE and Sjögren's syndrome, cytokine production originates in plasmacytoid dendritic cells (pDCs) under the influence of immune complexes formed by DNA and RNA from improperly removed apoptotic or necrotic cells, together with IgG autoantibodies. We studied the role of soluble factors in the serum or cerebrospinal fluid (CSF) of AGS patients and their capacity to stimulate pDCs to produce IFN-alpha. Our findings show that, in contrast to SLE, there is no decrease in the number of circulating pDCs in AGS patients. Secondly, unlike the autoantibodies in the serum of patients with SLE or Sjögren's syndrome, there is no increased frequency of antinuclear antibodies (ANA) or other soluble factors inducing IFN-alpha from pDCs. These data indicate that the origin of IFN-alpha in AGS is different from that in the autoimmune diseases tested.