Treatment of autoimmune diseases has relied on the use of broad immunosuppressant agents that, while delivering symptomatic relief, are not targeted to the underlying molecular mechanism. Therefore, they lack disease-modifying effects. Available therapies have significant long-term side effects, and, because of their untargeted and immunosuppressive nature, they interfere with defense mechanisms necessary to fight pathogens and malignancies. Targeting the loss of tolerance to self- or immunogenic antigens, which is the cause of autoimmune antigen-driven diseases, represents a paradigm shift in the treatment of those diseases.