New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory

Abstract

Takayasu arteritis (TAK) is a chronic vasculitis that mainly affects the aorta, its major branches, and the pulmonary arteries. Since the description of the first case by Mikito Takayasu in 1908, several aspects of this rare disease, including the epidemiology, diagnosis, and the appropriate clinical assessment, have been substantially defined. Nevertheless, while it is well-known that TAK is associated with a profound inflammatory process, possibly rooted to an autoimmune disorder, its precise etiology has remained largely unknown. Efforts to identify the antigen(s) that trigger autoimmunity in this disease have been unsuccessful, however, it is likely that viruses or bacteria, by a molecular mimicry mechanism, initiate or propagate the auto-immune process in this disease. In this article, we summarize recent advances in the understanding of TAK, with emphasis on new insights related to the pathogenesis of this entity that may contribute to the design of novel therapeutic approaches.

Keywords: Tertiary lymphoid organ; autoimmune diseases; microbiome; molecular mimicry; pulseless diseases; vasculitis.

Figure 1

Current understanding of the pathogenesis of Takayasu arteritis.

Figure 2

Potential role of pathogenic or commensal microbes in the pathogenesis of Takayasu arteritis. (A) Gut microbiota. A normal gut microbiota contributes to the development and education of the immune system, which is essential for the maintenance of physiologic homeostasis. Conversely, in the presence of dysbiosis, the number and function of regulatory T-cells are impaired and hyperactive cytotoxic T cells may grow without control, consequently the immune equilibrium is lost. The growing of pathogenic bacteria in the gut, likely harboring antigens that resemble antigens expressed by aortic or vascular tissues of the host, may promote the sensitization of the immune cells to the host own antigens, via molecular mimicry leading to autoimmunity. (B) Vascular microbiota. The colonization of pathogenic bacteria in aortic tissues may promote a local immune reaction against pathogen proteins and recruited immune cells may cross-react with antigens expressed in normal tissues leading to autoimmunity.