New horizons for human pathogenic autoantibodies

Pathogenic autoantibodies directed against secreted or membrane-associated autoantigens cause disease mainly by disrupting the function of target proteins or by promoting the destruction of cells expressing these cell-surface molecules. In the past decade, many new pathogenic autoantibodies have been identified in different autoimmune diseases. Here we describe several examples of autoimmune conditions caused by pathogenic autoantibodies against targets such as receptors, channels, and cell surface proteins in neurological diseases, glomerular proteins in kidney diseases, and various cytokines in pulmonary disease and acquired immunodeficiencies. The clinical features of these diseases, the structural and functional diversity of the target proteins, and methods used for autoantibody detection are discussed. Further study of pathogenic autoantibodies, particularly defining the full spectrum of target proteins, may uncover previously uncharacterized diseases, as well as generate new diagnostic and treatment options.