Takayasu's arteritis pathophysiology

The pathogenesis of Takayasu’s arteritis is poorly understood. Takayasu’s arteritis characterized by segmental and patchy granulomatous inflammation of the aorta and its major derivative branches.This inflammation leads to arterial stenosis, thrombosis, and aneurysms. Three factors that have been suggested to have association with susceptibility, development and progression of Takayasu’s arteritis are genetic influences, immunologic mechanisms, and relationship to tuberculosis. The most important conditions associated with Takayasu’s arteritis include ankylosing spondylitis, inflammatory bowel disease, and Behçet’s syndrome. On gross pathology, stiff and rigid aorta on palpation, gelatinous appearance of thickened adventitia, and sharp line of demarcation between normal and diseased segments might be seen. On microscopic histopathological analysis characteristic findings of Takayasu’s arteritis include inflammation around the vasa vasorum and at the medio-adventitial junction, edema of the media and adventitia, giant cell granulomatous reaction, laminar necrosis, and fragmentation of elastic fibers.

• The pathogenesis of Takayasu’s arteritis is poorly understood.^[1]
• Granulomatous inflammation of the aorta and its major branches might lead to Takayasu’s arteritis.
• Cell-mediated mechanisms are considered as a main pathogenesis mechanism of Takayasu’s arteritis and it is similar to giant cell arteritis.
• This inflammation leads to arterial stenosis, thrombosis, and aneurysms.
• Irregular fibrosis of the blood vessels due to chronic vasculitis may lead to intimal fibrosis.
• There are three factors that have associated with disease susceptibility, development and progression:
  • Relationship to tuberculosis (TB)
  • Genetic influences
  • Immunologic mechanisms

Relationship to tuberculosis (TB)

• It has been suggested that Takayasu arteritis is associated with TB. Following evidences support this hypothesis:^[2]

• • Granulomatous inflammation with the Langhans-type of giant cells in many cases of Takayasu arteritis
  • Intermittent coexistence of Takayasu arteritis with pulmonary and extrapulmonary tuberculosis
  • Hypersensitivity to the tuberculosis organism

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 leukocyte antigen (HLA) alleles in different populations. In Japan and Korea, there is a clear association with the extended haplotype:^[3]
  • HLA-B*52
  • HLA-DRB1*1502
  • HLA-DRB5*0102
  • HLA-DQA1*0103
  • HLA-DQB1*0601
  • HLA-DPA1*02
  • HLA-DPB1*0901

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.
• It has been 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.

• The most important conditions associated with Takayasu’s arteritis include:
  • Ankylosing spondylitis
  • Inflammatory bowel disease (IBD)
  • Behçet’s syndrome

On gross pathology characteristic findings of Takayasu’s arteritis are as follows:^[5]

• Stiff and rigid aorta on palpation
• Gelatinous appearance of thickened adventitia
• Enlarged para-aortic lymph nodes in the area of renal and subclavian arteries
• Sharp line of demarcation between normal and diseased segments

On microscopic histopathological analysis characteristic findings of Takayasu’s arteritis are as follows:^[5]

• Inflammation around the vasa vasorum and at the medio-adventitial junction
• Edema of the media and adventitia
• Giant cell granulomatous reaction
• Laminar necrosis
• Fragmentation of elastic fibers
• Rapid or more severe inflammation leads to:
  • Loss of smooth muscle cells
  • Medial weakening
  • Vascular dilatation
  • Aneurysm formation

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