Can we cure autoimmunity?

Autoimmune diseases have, until recently, been treated with relatively broad immunosuppressive regimens. Newer, more focused monoclonal antibody therapies directed to specific targets, for example, anti-TNF or anti-B cell therapies, can produce significant immunosuppression. 'Remission' of autoimmune disease that requires ongoing immunosuppression is not an ideal solution. We define a 'cure' for autoimmunity as: resolution of disease without ongoing immunosuppressive therapy. Herein, we discuss the possibilities of such a cure, the mechanisms behind such approaches, and obstacles in the setting of representative systemic (systemic lupus erythematosus, or SLE) and organ-specific (type 1 diabetes, T1D) autoimmune diseases. 'Cure' of autoimmunity is a remarkably difficult goal and, as illustrated here, will require detailed scientific understanding of each autoimmune disease, even beyond the remarkable advances achieved to date. The basic distinction between autoimmune diseases, in which the target organ is largely destroyed at clinical onset (e.g. T1D), and systemic diseases affecting multiple organs strongly affects how progress can be made towards a cure. In the case of systemic disease, obtaining exact further knowledge of the role of immune cell subsets (e.g. short-lived plasma cells in SLE) is critical. In organ-specific autoimmunity, such as in T1D, improved preclinical detection and characterization of the preclinical immune pathology will be essential.