Intracellular C3 system dysregulation contributes to human autoimmune diseases such as scleroderma, systemic lupus erythematosus (SLE), RA, and multiple sclerosis, as pathological intracellular C3 hyperactivation contributes to Th1 hyperactivity in these autoimmune conditions (4, 30). The gene discussed is C3; the disease is scleroderma.