Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review

•Genetic factors and proper inciting events play important roles in loss of tolerance.•The presence of autoantibodies is a hallmark of many autoimmune diseases.•Autoantibodies can appear long before the onset of many autoimmune diseases.•Autoantibodies can be used to predict a future autoimmune disease in some cases.

The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. Both humoral and cellular elements of the adaptive immune system play a role in the pathogenesis of autoimmune diseases and the presence of autoantibodies have been detected in most but not all autoimmune diseases before the appearance of clinical symptoms. In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well. This observation is intriguing because it suggests that we can, to some degree, predict who may or may not develop autoimmune diseases. However, the role of autoantibodies in the pathogenesis of autoimmune diseases, whether they actually affect disease progression or are merely an epiphenomenon is still not completely clear in many autoimmune diseases. Because of these gaps in our knowledge, the ability to accurately predict a future autoimmune disease can only be considered a relative risk factor. Importantly, it raises the critical question of defining other events that may drive a patient from a preclinical to a clinical phase of disease.