Self-reactivity against stress-induced cell molecules: the missing link between Takayasu's arteritis and tuberculosis?

Takayasu's arteritis (TA) is a chronic, occlusive, inflammatory disease of the aorta, its major branches and the pulmonary arteries. Its etiology remains unclear, although it has been suggested that a variety of antigens from Mycobacterium tuberculosis and probably other mycobacteria may trigger inflammatory pathology either directly in the arterial wall or remote from the actual location of mycobacterial infection, possibly through molecular mimicry mechanisms. However, recent evidence showing absence of both mycobacteria directly into arterial tissue as well as latent M. tuberculosis infection is challenging this notion. The hypothesis offered in this manuscript postulates that the lost of tolerance against self stress proteins is a primal pathogenic event in TA with the innate immune system as key culprit in the initiation and amplification of inflammatory response, while the extensive sequence homology between mycobacterial and human stress proteins leads to epiphenomenal cross-reactions mediated by adaptive immune system. If it is so, this postulate reconciles epidemiological, immunological and genetic linkage between TA and mycobacteria, while supporting the widespread Bacille Calmette-Guérin (BCG) vaccination worldwide and giving rationale to a safety use of anti-tumor necrosis factor (TNF) therapy in patients with TA.