Mycobacterium tuberculosis heat shock proteins and autoimmunity in sarcoidosis

Sarcoidosis (SA) is a granulomatous disorder of an unknown etiology. Infectious, genetic factors and autoimmunity have been explored as potential causes of SA. Pathologic similarities between SA and tuberculosis (TB) suggest Mycobacterium tuberculosis, especially mycobacterial antigen(s) e.g. heat shock proteins (Mtb-hsp) as causative factors. Mtb-hsp, especially Mtb-hsp65, may provide a link between infection and autoimmunity by cross-reactivity between the mycobacterial and human hsp. There is 100% homology between M. tuberculosis and Mycobacterium bovis BCG hsp. In light of evidences necessary to establish SA which is autoimmune in origin, my recently published findings prompted me to raise the hypothesis that, in genetically different individuals, the same antigens (Mtb-hsp) may induce different immune responses, leading to the development of SA or TB. The hypothesis seems to have been supported by an epidemiological analysis of the worldwide SA and TB prevalences that reveal that the TB distribution is approximately opposite to that of SA. Because one third of the Earthʹs population has been infected with M. tuberculosis, it is possible that the presence of mycobacterial infection or BCG vaccination (e.g., Mtb-hsp65) in genetically predisposed host may be involved in the development of autoimmunity.