Pro: Evidence for a Primary Lesion in the Target Organ in Autoimmune Disease

Despite nearly 40 years of organ specific autoimmunity research, a question of whether the immune response in autoimmunity is due to dysregulation of the immune system or to a primary lesion in the target organ remains unresolved. Strength in the immune dysregulation argument, for which there has never been direct evidence in man, has largely derived from failure to identify a primary lesion to account for it. That is, until recently. Just as inflammation was considered a primary cause of disease until microbes were discovered, so autoimmunity was looked upon as a state of immune dysregulation until the equivalent of microbes were discovered. The microbe equivalents are viral particles, expressed on the surface of target organ cells under certain circumstances, and often encoded in the host's genome. These neo-antigens induce a protective, rather than aggressive immune response and account for the very singular target specificity observed, for example in the beta cell destruction of type 1 diabetes.