TREX1 and systemic lupus erythematosus: Numerous studies have shown that loss-of-function mutations in TREX1 lead to abnormal accumulation of cytoplasmic DNA, which in turn over-activates the natural immune response and ultimately leads to the development of autoimmune diseases, including systemic lupus erythematosus and vascular diseases, retinopathy, and cerebral leukoencephalopathy (59, 60).