Review articleTakayasu's arteritis: An update on physiopathology
Introduction
Takayasu's arteritis (TA) is a chronic large vessel vasculitis that predominantly affects elastic arteries such as the aorta, its major division branches, and the pulmonary arteries [1], [2]. It is most common in Asian and South American individuals, and it affects young females more frequently than males. Its clinical manifestations vary, depending on the topography, the type of vascular lesions, and whether the inflammation is persistent or not. The etiology of TA is still unknown, but infectious agents [2], genetic factors, and autoimmunity are thought to play a major role in the physiopathology of this disease [3]. Treatment strategy is based on corticosteroids and other immunosuppressive agents, but some patients may require surgical or endovascular revascularization procedures. From a pathogenic point of view, T-cell-dependent immunity, chemokine- and cytokine-dependent immunity and, less clearly, B-cell-dependent immunity are the main pathogenic mechanisms leading to the arterial wall injury.
Section snippets
T-cell-dependent vasculitic inflammation in Takayasu's arteritis
Cell-mediated autoimmunity has been clearly implicated in the physiopathology of vascular cell injury in TA over the last 20 years. Immunohistochemical studies of the infiltrating cells in the aortic tissue of patients with TA have shown that they mainly consisted of gamma–delta T-cells, NK cells, cytotoxic T-cells, T-helper cells, and macrophages, suggesting a role for these cells in the physiopathology of the disease [4].
Some allelic variant of class II antigen-presenting HLA molecules
Arterial wall inflammation in Takayasu's arteritis
The inflammatory lesions in TA are produced in the media and adventitia through the vasa vasorum and not the macroendothelium, thus requiring an activation of vasa vasorum endothelial cells to allow the lymphocytes to gain access to the arterial wall [24]. The plasma level of soluble vascular cell adhesion molecule-1 (sVCAM1) is elevated in TA [25]. Intercellular adhesion molecule-1 (ICAM1) and HLA classes I and II are upregulated in the aortic tissue and may facilitate the recognition and
Chemokine and cytokine-dependent vasculitic inflammation in Takayasu's arteritis
Interleukin (IL)-6 is a pro-inflammatory cytokine that is mainly synthesized by macrophages, activated monocytes, and T-cells. It activates B-cells, enhances T-cell cytotoxicity [29], NK cell activity [30], and fibroblast proliferation, and it induces acute-phase protein synthesis [31]. RANTES (regulated on activation, normal T-cell-expressed and secreted) and IL-8 are, respectively, a chemokine and a cytokine that have a strong chemoattractant activity for most mononuclear cells, like the ones
B-cell-dependent vasculitic inflammation in Takayasu's arteritis
Whether humoral immunity takes part in the physiopathology of TA is not clear. The presence of immune complexes, both in sera and on lymphocyte Fc receptors, has been reported [38] in some cases but remains controversial [39]. Anti-aorta antibodies have long been reported in TA [40], [41], [42], [43], but some authors also found conflicting results [44]. Dhingra et al. reported that the mean value of anti-aorta antibody titer in 30 patients suffering from TA was significantly higher than that
Conclusion
The physiopathology of TA is complex and multifactorial. It clearly appears that TA is an autoimmune disease in which cellular immunity plays a major role and humoral immunity a role that still remains to be elucidated. In 2004, Seko et al. postulated a pathogenic sequence linking up some of the data discussed above (Fig. 1) [19]. It now appears more clearly that stimulation from an antigen of unknown nature, possibly infectious, could trigger HSP-65 expression in aortic tissue which, in turn,
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