Takayasu's arteritis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Farnaz Khalighinejad, MD [2]
Overview
Pathophysiology
- The pathogenesis of Takayasu's arteritis is poorly understood.[1]
- Takayasu's arteritis characterized by segmental and patchy granulomatous inflammation of the aorta and its major derivative branches.
- Cell-mediated mechanisms are thought to be of primary importance and may be similar to those in giant cell arteritis.
- This inflammation leads to arterial stenosis, thrombosis, and aneurysms.
- There is also irregular fibrosis of the blood vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis.
- Three factors have been suggested that have associated with disease susceptibility, development and progression:
- Relationship to tuberculosis (TB)
- Genetic influences
- Immunologic mechanisms
Relationship to tuberculosis (TB)
Granulomatous inflammation with the Langhans-type of giant cells in many cases of Takayasu arteritis and the intermittent coexistence of Takayasu arteritis with pulmonary and extrapulmonary tuberculosis, support this idea. However,the absence of mycobacterial organisms in arteritic lesions and the lack of response to anti-tuberculus therapy suggest that perhaps hypersensitivity to the tuberculus organism may play a role in the pathogenesis of Takayasu arteritis.[2]
Genetic influences
Geographic distribution of Takayasu arteritis, with high prevalence in Japan and Korea, suggests that genetic factors are probably play a role in the pathogenesis of Takayasu arteritis.
- Takayasu arteritis has been associated with different human leucocyte antigen (HLA) alleles in different populations.
- In Japan and Korea there is a clear association with the extended haplotype: HLA B*52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601, DPA1*02-DPB1*0901.[3]
Immunologic mechanisms
Because of rheumatic-type complaints in many Takayasu arteritis patients, the relationship between Takayasu arteritis and autoimmune and collagen vascular disorders has been suggested.
- Immunohistopathologic examination has shown that the infiltrating cells in aortic tissue mainly consist of killer cells, especially gamma delta T lymphocytes.
- These cells may cause vascular injury by releasing large amounts of the cytolytic compound perforin.
- Seko et al have reported that γδT cells, αβT cells (CD4 and CD8), and natural killer cells play an important role in the vascular injury.[4]
- No specific autoantigens have yet been identified.
Associations
- The most important conditions associated with Takayasu's arteritis include:
Gross pathology
On gross pathology of Takayasu's arteritis:
- The aorta feels stiff and rigid on palpation
- In the early stages of the disease, the thickened adventitia may have a gelatinous appearance
- Presence of enlarged para-aortic lymph nodes, particularly in the area of renal and subclavian arteries
- The intimal fibrocellular hyperplasia is seen as plaques, and depending on the amounts of acid mucopolysaccharides and collagen, it appears gelatinous or white
- Sometimes the involvement is seen as diffuse intimal thickening with mild affection of the adventitia
- Localized disease is often seen in children and there is always a sharp line of demarcation between normal and diseased segments
- Superimposed calcification and atherosclerosis increase the vascular rigidity
Microscopic pathology
On microscopic histopathological analysis:
- The initial site of inflammation is around the vasa vasora and at the medio-adventitial junction.
- There is edema, and mononuclear cell infiltration (CD4 and CD8 lymphocytes, plasma cells, and macrophages) in the outer thirds of the media and adventitia.
- Giant cell granulomatous reaction and laminar necrosis can also be present.
- Fragmentation of elastic fibers with “elasticophagia” is prominent
- Rapid or more severe inflammation leads to loss of smooth muscle cells, medial weakening, vascular dilatation, and even aneurysm formation
- There is reactive fibrosis and increased ground substance in the intima, with overlying layer of thrombus or a band of neo-vascularization at the intimo-medial junction.
References
- ↑ Inder SJ, Bobryshev YV, Cherian SM, Wang AY, Lord RS, Masuda K, Yutani C (March 2000). "Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions". Cardiovasc Surg. 8 (2): 141–8. PMID 10737351.
- ↑ Lupi-Herrera E, Sánchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE (January 1977). "Takayasu's arteritis. Clinical study of 107 cases". Am. Heart J. 93 (1): 94–103. PMID 12655.
- ↑ Salazar M, Varela A, Ramirez LA, Uribe O, Vasquez G, Egea E, Yunis EJ, Iglesias-Gamarra A (August 2000). "Association of HLA-DRB1*1602 and DRB1*1001 with Takayasu arteritis in Colombian mestizos as markers of Amerindian ancestry". Int. J. Cardiol. 75 Suppl 1: S113–6. PMID 10980348.
- ↑ Seko Y, Takahashi N, Tada Y, Yagita H, Okumura K, Nagai R (August 2000). "Restricted usage of T-cell receptor Vgamma-Vdelta genes and expression of costimulatory molecules in Takayasu's arteritis". Int. J. Cardiol. 75 Suppl 1: S77–83, discussion S85–7. PMID 10980341.