Functional autoantibodies: Definition, mechanisms, origin and contributions to autoimmune and non-autoimmune disorders

A growing body of evidence underscores the relevance of functional autoantibodies in the development of various pathogenic conditions but also in the regulation of homeostasis. However, the definition of functional autoantibodies varies among studies and a comprehensive overview on this emerging topic is missing. Here, we do not only explain functional autoantibodies but also summarize the mechanisms underlying the effect of such autoantibodies including receptor activation or blockade, induction of receptor internalization, neutralization of ligands or other soluble extracellular antigens, and disruption of protein-protein interactions. In addition, in this review article we discuss potential triggers of production of functional autoantibodies, including infections, immune deficiency and tumor development. Finally, we describe the contribution of functional autoantibodies to autoimmune diseases including autoimmune thyroid diseases, myasthenia gravis, autoimmune pulmonary alveolar proteinosis, autoimmune autonomic ganglionopathy, pure red cell aplasia, autoimmune encephalitis, pemphigus, acquired thrombotic thrombocytopenic purpura, idiopathic dilated cardiomyopathy and systemic sclerosis, as well as non-autoimmune disorders such as allograft rejection, infectious diseases and asthma.