Autoimmune diseases are characterized by the presence of serum autoantibodies of various specificities but the significance of these autoantibodies in the development of symptoms is unclear. Most studies have been carried out using polyclonal sera. However, antibodies’ effects depend on Fab-mediated diversity in epitope specificity, and also on Fc-mediated effects dependent on immunoglobulin class and subclass, immune complex-induced activation of complement, and the milieu in which the reaction occurs. Monoclonal autoantibodies have rarely been studied, but increasingly such mAb are becoming available. These include human mAb to GAD65 from patients with newly diagnosed type 1 diabetes, and mouse mAb to type II collagen that have the capacity to induce collagen antibody induced arthritis (CAIA). In both systems, there is clear evidence that the epitope specificity of the antibodies is related to the expression of the disease, and protective antibodies may occur. © 2004 - 2023 Nova Science Publishers