Takayasu's arteritis pathophysiology: Difference between revisions
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* Cell-mediated mechanisms are thought to be of primary importance and may be similar to those in giant cell arteritis. | * 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]]. | ||
* 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 | |||
* 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 vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis. | ||
* 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.<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 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> | ||
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* 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.<ref name="pmid10980348">{{cite journal |vauthors=Salazar M, Varela A, Ramirez LA, Uribe O, Vasquez G, Egea E, Yunis EJ, Iglesias-Gamarra A |title=Association of HLA-DRB1*1602 and DRB1*1001 with Takayasu arteritis in Colombian mestizos as markers of Amerindian ancestry |journal=Int. J. Cardiol. |volume=75 Suppl 1 |issue= |pages=S113–6 |date=August 2000 |pmid=10980348 |doi= |url=}}</ref> | * 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.<ref name="pmid10980348">{{cite journal |vauthors=Salazar M, Varela A, Ramirez LA, Uribe O, Vasquez G, Egea E, Yunis EJ, Iglesias-Gamarra A |title=Association of HLA-DRB1*1602 and DRB1*1001 with Takayasu arteritis in Colombian mestizos as markers of Amerindian ancestry |journal=Int. J. Cardiol. |volume=75 Suppl 1 |issue= |pages=S113–6 |date=August 2000 |pmid=10980348 |doi= |url=}}</ref> | ||
The genetic contribution to the pathogenesis of Takayasu's arteritis is supported by the genetic association with HLA-B∗52. | * The genetic contribution to the pathogenesis of Takayasu's arteritis is supported by the genetic association with HLA-B∗52. | ||
* no specific autoantigens have yet been identified and for any adaptive immune response to occur, whether against exogenous or endogenous antigen, presentation of antigen to T cells in the context of the major histocompatibility complex is central. | |||
A recent large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing the number of genetic loci for this disease to five risk loci across the genome. About 200,000 genetic variants were genotyped in two ethnically divergent Takayasu's arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. The study identified and confirmed two independent susceptibility loci within the HLA region (r2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10-9). In addition, a genetic association was identified and confirmed between Takayasu's arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. In addition, a genetic association between IL12B and Takayasu arteritis was established (rs56167332, OR = 1.54, p = 2.18 × 10-8). A fifth genetic locus for the disease on chromosome 21q22 downstream of PSMG1 was also revealed (P=4.39X10-7) | A recent large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing the number of genetic loci for this disease to five risk loci across the genome. About 200,000 genetic variants were genotyped in two ethnically divergent Takayasu's arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. The study identified and confirmed two independent susceptibility loci within the HLA region (r2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10-9). In addition, a genetic association was identified and confirmed between Takayasu's arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. In addition, a genetic association between IL12B and Takayasu arteritis was established (rs56167332, OR = 1.54, p = 2.18 × 10-8). A fifth genetic locus for the disease on chromosome 21q22 downstream of PSMG1 was also revealed (P=4.39X10-7) | ||
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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.
- 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
- There is also irregular fibrosis of the blood vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis.
- 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.[2]
- Infection has been considered to play a role in the pathogenesis of Takayasu arteritis. Tuberculosis has been particularly implicated in view of the high prevalence of infection, past or present, in affected patients,largely from endemic areas.[3]
- 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.[4]
- The genetic contribution to the pathogenesis of Takayasu's arteritis is supported by the genetic association with HLA-B∗52.
- no specific autoantigens have yet been identified and for any adaptive immune response to occur, whether against exogenous or endogenous antigen, presentation of antigen to T cells in the context of the major histocompatibility complex is central.
A recent large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing the number of genetic loci for this disease to five risk loci across the genome. About 200,000 genetic variants were genotyped in two ethnically divergent Takayasu's arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. The study identified and confirmed two independent susceptibility loci within the HLA region (r2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10-9). In addition, a genetic association was identified and confirmed between Takayasu's arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. In addition, a genetic association between IL12B and Takayasu arteritis was established (rs56167332, OR = 1.54, p = 2.18 × 10-8). A fifth genetic locus for the disease on chromosome 21q22 downstream of PSMG1 was also revealed (P=4.39X10-7)
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.
- ↑ 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.
- ↑ 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.