|4.||Cell and Molecular Biology|
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects mostly young women. The disease pathogenesis remains poorly defined and specific treatments are not available. A hallmark in SLE disease is the development of antinuclear autoantibodies (ANA) which react with self-nuclear antigens. These antibodies form complexes with nuclear antigens exposed by necrotic cells and deposit in tissues to cause inflammation and tissue injuries. Understanding how ANA are induced is essential to developing targeted treatments.
We adopt immunologic, proteomics, cell biology and bioinformatics approaches to delineate how ANA are caused in SLE patients. We use complement C1q and C1r/C1s deficient models because these genetic deficiencies cause ANA.
We found that C1q/C1r/C1s together degrade nuclear antigens and nuclear DAMPs in necrotic cells which has brought us closer to the primary triggers of ANA.