Takayasu's arteritis pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
The pathogenesis of Takayasu's arteritis is poorly understood. Takayasu's arteritis characterized by segmental and patchy [[Granuloma|granulomatous]] [[inflammation]] of the aorta and its major derivative branches.This inflammation leads to | The [[pathogenesis]] of Takayasu's arteritis is poorly understood. Takayasu's arteritis characterized by segmental and patchy [[Granuloma|granulomatous]] [[inflammation]] of the [[aorta]] and its major derivative branches.This [[inflammation]] leads to [[Artery|arterial]] [[stenosis]], [[thrombosis]], and [[Aneurysm|aneurysms]]. Three factors that have been suggested to have association with susceptibility, development and progression of Takayasu's arteritis are [[Genetics|genetic]] influences, [[Immunology|immunologic]] mechanisms and relationship to [[tuberculosis]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
* The pathogenesis of Takayasu's arteritis is poorly understood.<ref name="pmid10737351">{{cite journal |vauthors=Inder SJ, Bobryshev YV, Cherian SM, Wang AY, Lord RS, Masuda K, Yutani C |title=Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions |journal=Cardiovasc Surg |volume=8 |issue=2 |pages=141–8 |date=March 2000 |pmid=10737351 |doi= |url=}}</ref> | * The [[pathogenesis]] of Takayasu's arteritis is poorly understood.<ref name="pmid10737351">{{cite journal |vauthors=Inder SJ, Bobryshev YV, Cherian SM, Wang AY, Lord RS, Masuda K, Yutani C |title=Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions |journal=Cardiovasc Surg |volume=8 |issue=2 |pages=141–8 |date=March 2000 |pmid=10737351 |doi= |url=}}</ref> | ||
* Takayasu's arteritis characterized by segmental and patchy [[Granuloma|granulomatous]] [[inflammation]] of the aorta and its major derivative branches. | * Takayasu's arteritis characterized by segmental and patchy [[Granuloma|granulomatous]] [[inflammation]] of the [[aorta]] and its major derivative branches. | ||
* [[Cell-mediated immunity|Cell-mediated]] mechanisms are thought to be of primary importance and may be similar to those in [[giant cell arteritis]]. | * [[Cell-mediated immunity|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 [[Aneurysm|aneurysms]]. | * This [[inflammation]] leads to arterial [[stenosis]], [[thrombosis]], and [[Aneurysm|aneurysms]]. | ||
* There is also irregular [[fibrosis]] of the blood vessels due to chronic [[vasculitis]], leading to sometimes massive intimal fibrosis. | * There is also irregular [[fibrosis]] of the [[Blood vessel|blood vessels]] due to chronic [[vasculitis]], leading to sometimes massive [[Tunica intima|intimal]] [[fibrosis]]. | ||
* Three factors have been suggested that have associated with disease susceptibility, development and progression: | * Three factors have been suggested that have associated with disease susceptibility, development and progression: | ||
** Relationship to [[tuberculosis]] (TB) | ** Relationship to [[tuberculosis]] (TB) | ||
** Genetic influences | ** [[Genetics|Genetic]] influences | ||
** Immunologic mechanisms | ** [[Immunology|Immunologic]] mechanisms | ||
'''Relationship to tuberculosis (TB)''' | '''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.<ref name="pmid12655">{{cite journal |vauthors=Lupi-Herrera E, Sánchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE |title=Takayasu's arteritis. Clinical study of 107 cases |journal=Am. Heart J. |volume=93 |issue=1 |pages=94–103 |date=January 1977 |pmid=12655 |doi= |url=}}</ref> | [[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 [[Arteritis|arteritic]] lesions and the lack of response to anti-tuberculus therapy suggest that perhaps [[hypersensitivity]] to the [[Tuberculosis|tuberculus]] organism may play a role in the [[pathogenesis]] of Takayasu arteritis.<ref name="pmid12655">{{cite journal |vauthors=Lupi-Herrera E, Sánchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE |title=Takayasu's arteritis. Clinical study of 107 cases |journal=Am. Heart J. |volume=93 |issue=1 |pages=94–103 |date=January 1977 |pmid=12655 |doi= |url=}}</ref> | ||
'''Genetic influences''' | '''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. | Geographic distribution of Takayasu arteritis, with high [[prevalence]] in Japan and Korea, suggests that [[Genetics|genetic]] factors are probably play a role in the [[pathogenesis]] of Takayasu arteritis. | ||
* Takayasu arteritis has been associated with different [[Human leukocyte antigen|human leucocyte antigen]] ([[Human leukocyte antigen|HLA]]) alleles in different populations. | * Takayasu arteritis has been associated with different [[Human leukocyte antigen|human leucocyte antigen]] ([[Human leukocyte antigen|HLA]]) alleles in different populations. | ||
| Line 30: | Line 30: | ||
'''Immunologic mechanisms''' | '''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. | Because of rheumatic-type complaints in many Takayasu arteritis patients, the relationship between Takayasu arteritis and [[Autoimmunity|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]]. | * Immunohistopathologic examination has shown that the infiltrating cells in [[Aorta|aortic]] tissue mainly consist of [[Natural killer cell|killer cells]], especially gamma delta [[T lymphocytes]]. | ||
* These cells may cause vascular injury by releasing large amounts of the cytolytic compound [[perforin]]. | * 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 cell|natural killer cells]] play an important role in the vascular injury.<ref name="pmid10980341">{{cite journal |vauthors=Seko Y, Takahashi N, Tada Y, Yagita H, Okumura K, Nagai R |title=Restricted usage of T-cell receptor Vgamma-Vdelta genes and expression of costimulatory molecules in Takayasu's arteritis |journal=Int. J. Cardiol. |volume=75 Suppl 1 |issue= |pages=S77–83; discussion S85–7 |date=August 2000 |pmid=10980341 |doi= |url=}}</ref> | * Seko ''et al'' have reported that γδT cells, αβT cells (CD4 and CD8), and [[Natural killer cell|natural killer cells]] play an important role in the [[vascular injury]].<ref name="pmid10980341">{{cite journal |vauthors=Seko Y, Takahashi N, Tada Y, Yagita H, Okumura K, Nagai R |title=Restricted usage of T-cell receptor Vgamma-Vdelta genes and expression of costimulatory molecules in Takayasu's arteritis |journal=Int. J. Cardiol. |volume=75 Suppl 1 |issue= |pages=S77–83; discussion S85–7 |date=August 2000 |pmid=10980341 |doi= |url=}}</ref> | ||
* No specific [[Autoantigen|autoantigens]] have yet been identified. | * No specific [[Autoantigen|autoantigens]] have yet been identified. | ||
== Associations == | == Associations == | ||
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** [[Behçet's disease|Behçet's syndrome]](BS) | ** [[Behçet's disease|Behçet's syndrome]](BS) | ||
== Gross pathology == | == Gross pathology == | ||
On gross pathology of Takayasu's arteritis:<ref name="pmid10980333">{{cite journal |vauthors=Gravanis MB |title=Giant cell arteritis and Takayasu aortitis: morphologic, pathogenetic and etiologic factors |journal=Int. J. Cardiol. |volume=75 Suppl 1 |issue= |pages=S21–33; discussion S35–6 |date=August 2000 |pmid=10980333 |doi= |url=}}</ref> | On [[gross pathology]] of Takayasu's arteritis:<ref name="pmid10980333">{{cite journal |vauthors=Gravanis MB |title=Giant cell arteritis and Takayasu aortitis: morphologic, pathogenetic and etiologic factors |journal=Int. J. Cardiol. |volume=75 Suppl 1 |issue= |pages=S21–33; discussion S35–6 |date=August 2000 |pmid=10980333 |doi= |url=}}</ref> | ||
* The [[aorta]] feels stiff and rigid on palpation | * The [[aorta]] feels stiff and rigid on [[palpation]] | ||
* In the early stages of the disease, the thickened [[adventitia]] may have a gelatinous appearance | * In the early stages of the disease, the thickened [[adventitia]] may have a gelatinous appearance | ||
* Presence of enlarged [[Paraaortic lymph node|para-aortic]] lymph nodes, mainly in the area of [[Renal artery|renal]] and [[Subclavian artery|subclavian arteries]] | * Presence of enlarged [[Paraaortic lymph node|para-aortic]] [[Lymph node|lymph nodes]], mainly in the area of [[Renal artery|renal]] and [[Subclavian artery|subclavian arteries]] | ||
* The intimal fibrocellular [[hyperplasia]] is seen as plaques, and depending on the amounts of acid [[mucopolysaccharide | * The [[Tunica intima|intimal]] fibrocellular [[hyperplasia]] is seen as [[Plaque|plaques]], and depending on the amounts of acid [[Glycosaminoglycan|mucopolysaccharide<nowiki/>s]] and [[collagen]], it appears gelatinous or white | ||
* Sometimes the involvement is seen as diffuse intimal thickening with mild affection of the [[adventitia]] | * Sometimes the involvement is seen as diffuse [[Tunica intima|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 | * 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 | * Superimposed [[calcification]] and [[atherosclerosis]] increase the [[vascular]] rigidity | ||
== Microscopic pathology == | == Microscopic pathology == | ||
On microscopic histopathological analysis:<ref name="pmid10980333" /> | On microscopic histopathological analysis:<ref name="pmid10980333" /> | ||
* The initial site of [[inflammation]] is around the vasa vasora and at the medio-adventitial junction | * The initial site of [[inflammation]] is around the [[Vasa vasorum|vasa vasora]] and at the [[Tunica media|medio]]-[[Adventitia|adventitial]] junction | ||
* There is edema, and [[mononuclear cell]] infiltration ([[CD4]] and [[CD8]] [[Lymphocyte|lymphocytes]], [[Plasma cell|plasma cells]], and [[Macrophage|macrophages]]) in the outer thirds of the media and adventitia | * There is [[edema]], and [[mononuclear cell]] infiltration ([[CD4]] and [[CD8]] [[Lymphocyte|lymphocytes]], [[Plasma cell|plasma cells]], and [[Macrophage|macrophages]]) in the outer thirds of the [[Tunica media|media]] and [[adventitia]] | ||
* Giant cell granulomatous reaction and [[laminar necrosis]] can also be present | * [[Large cell|Giant cell]] [[Granuloma|granulomatous]] reaction and [[laminar necrosis]] can also be present | ||
* [[Fragmentation (biology)|Fragmentation]] of [[Elastic fiber|elastic fibers]] with “elasticophagia” is prominent | * [[Fragmentation (biology)|Fragmentation]] of [[Elastic fiber|elastic fibers]] with “elasticophagia” is prominent | ||
* Rapid or more severe inflammation leads to loss of [[smooth muscle cell]]<nowiki/>s, medial weakening, vascular dilatation, and even [[aneurysm]] formation | * Rapid or more severe [[inflammation]] leads to loss of [[smooth muscle cell]]<nowiki/>s, [[Tunica media|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 [[Neovascularization|neo-vascularization]] at the intimo-medial junction | * There is reactive [[fibrosis]] and increased ground substance in the [[intima]], with overlying layer of [[thrombus]] or a band of [[Neovascularization|neo-vascularization]] at the [[Tunica intima|intimo]]-[[Tunica media|medial]] junction | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 14:24, 27 April 2018
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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
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.
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:[5]
- 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, mainly 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:[5]
- 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.
- ↑ 5.0 5.1 Gravanis MB (August 2000). "Giant cell arteritis and Takayasu aortitis: morphologic, pathogenetic and etiologic factors". Int. J. Cardiol. 75 Suppl 1: S21–33, discussion S35–6. PMID 10980333.