Directing Autoimmunity to Nucleoprotein Particles : The Impact of Dendritic Cells and Interferon α in Lupus

Over half a million people in the United States have systemic lupus. Most are women in their childbearing years. They usually have arthritis and scarring rashes, and about half have kidney involvement that may progress to renal failure. With time, there is an increasing likelihood that the brain will be involved, often resulting in loss of cognitive ability, seizures, and psychosis. Although the clinical features are highly variable, the patients are unified by the constant presence of autoimmunity to nucleoproteins, particularly to chromatin and small nuclear RNA-protein particles such as the U series of snRNPs that mediate premessenger RNA processing, and the Ro antigen (1). The resulting autoantibodies account for much of the tissue injury. For example, anti-DNA antibodies are harmful because they form immune complexes with extra cellular DNA and trigger an Arthus type of tissue injury, and sometimes they cross-react with...