Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells

Patients with active SLE often have an ongoing production of IFN-alpha. We therefore searched for an endogenous IFN-alpha-inducing factor (IIF) in SLE patients and found that their sera frequently induced production of IFN-al pha in cultures of peripheral blood mononuclear cells (PBMC) from healthy b lood donors, especially when the PBMC were costimulated with the cytokines IFN-alpha 2b and granulocyte-macrophage colony-stimulating factor (GM-CSF). The phenotype of the IFN-alpha- producing cells (IPC) as determined by flo w cytometry corresponded to that of the natural IPC, resembling immature de ndritic cells. The IIF activity in SLE sera was sometimes as high as that o f a virus and was present especially in patients with active disease and wi th measurable IFN-alpha levels in serum. The IIF had an apparent molecular weight of 300-1000 kD and appeared to consist of both immunoglobulin and DN A, possibly being immune complexes. This endogenous IFN-alpha inducer may b e of pathogenic significance, since a reported occasional adverse effect of IFN-alpha therapy in patients with non-autoimmune disorders is development of anti-dsDNA antibodies and SLE.