Genetic and Environmental Modifiers Of Autoimmune Disease

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

The main focus of our group is the identification of characterization of genes and environmental factors that contribute to the development of systemic autoimmune disease. We use mouse models of systemic lupus erythematosus (SLE) to determine the necessity of certain molecular pathways and cellular interactions in the spontaneous autoimmune pathology. In addition, we analyze the effect of external influences, such as infections, in the progression of SLE. New mechanistic insight obtained from these studies can guide future therapeutic strategies to treat SLE in human patients. We previously described mice deficient in the IgG receptor FcgammaRIIB as a well-established murine model for SLE. Characterization of other genetic modifiers of SLE in the FcgammaRIIB-deficient line allowed us to determine that several genes linked to anti-viral RNA sensors including TLR7, MDA5 and MAVS, were susceptibility factors for autoimmune disease. This concept has been validated by multiple groups that work with mouse models and human SLE patients. As part of our investigation centered on environmental factors, in collaboration with other members of the NIAID Malaria Research Program we investigated interactions between infections and autoimmune disease. We examined the relationship between autoantibodies present at a healthy baseline and the subsequent risk of clinical malaria.