Recent studies of patients with systemic lupus erythematosus, together with data from lupus-prone mice, suggest that inappropriate activation of type I interferon might have a role in disease pathogenesis. Serum levels of IFN-α are elevated in SLE patients, and gene expression profiling of peripheral blood cells shows that most lupus cases demonstrate an upregulation of IFN-responsive genes. Of interest, the IFN gene 'signature' correlates with more severe disease. The available data support a model whereby chromatin-containing immune complexes circulating in the blood of lupus patients stimulate leukocytes to produce IFN, which perpetuates disease. These emerging insights into the connection between IFN and lupus provide a host of new diagnostic and therapeutic opportunities.
Bibliographical noteFunding Information:
We are grateful to the patients and their referring physicians for participation in these studies. We apologize to colleagues whose work we were unable to cite due to page limitations. This work was supported by grants and contracts from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Allergy and Infectious Diseases (NIAID), the Alliance for Lupus Research, the Mary Kirkland Center for Lupus Research, and the Minnesota Lupus Foundation.