Materiały źródłowe

• #1 Takayasu Arteritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459127/

  Takayasu arteritis, aka pulseless disease, is a systemic inflammatory condition which leads to damage of the medium and large arteries and their branches. […] An abnormality in cell-mediated immunity seems to be its main pathogenesis, but its etiology is still largely unknown. […] At its core it is characterized as an inflammatory granulomatous vasculitis of medium and large arteries, which leads to transmural fibrous thickening of the arterial walls, leading to multiple vascular obstructions and eventual ischemic changes. […] Cell-mediated immunity involving CD4+ and CD8+ T cells may play a key role in the pathophysiology of Takayasu arteritis, as these cells support the formation of granulomas and potentially activate the activities of various proteases such as matrix metalloproteinase (MMP), as well as other cells which promote chronic inflammation and fibrosis formation. […] There continues to be a substantial lack of understanding of the pathogenesis of Takayasu arteritis, and the etiology is largely unknown.

• #2 Takayasu’s arteritis – a comprehensive review

  https://www.rarediseasesjournal.com/articles/takayasus-arteritis–a-comprehensive-review.html

  Takayasus arteritis (TA) is a chronic inflammatory disease of unknown aetiology. The mechanism of this disease is not exactly defined. The inflammatory process is generally (but not exclusively) initiated in the second or third decade of life through the actions of non-specific inflammatory cells. As the disease progresses, fibrotic stenosis occurs in aorta and its main branches. The consequence of this inflammatory process can be stenosis, thrombosis, dilatation or aneurysm formation in aorta and/ or its branches. […] Takayasu arteritis (TA) is a large vessel vasculitis (LVV) characterized by granulomatous inflammation of the vessel wall with an unknown etiopathogenesis. TA predominantly affects young females during the second or third decades of life and mainly involves the aortic arch and its primary branches, ascending aorta, thoracic descending aorta and abdominal aorta. Early in the disease course, inflammation of the involved arteries progresses, resulting in segmental stenosis, occlusion, dilatation and/or aneurysm. This may cause extremity pain, claudication, bruits, absent or diminished pulses and loss of blood pressure.

• #3 Takayasu’s arteritis – Wikipedia

  https://en.wikipedia.org/wiki/Takayasu%27s_arteritis

  Takayasu’s arteritis (TA), also known as aortic arch syndrome, nonspecific aortoarteritis, and pulseless disease, is a form of large vessel granulomatous vasculitis with massive intimal fibrosis and vascular narrowing, most commonly affecting young or middle-aged women of Asian descent, though anyone can be affected. […] Although the cause of Takayasu arteritis is unknown, the condition is characterized by segmental and patchy granulomatous inflammation of the aorta and its major derivative branches. This inflammation leads to arterial stenosis, thrombosis, and aneurysms. […] The genetic contribution to the pathogenesis of Takayasu’s arteritis is supported by the genetic association with HLA-B·52. A 2013 large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing its number of genetic loci to five risk loci across the genome.

• #4 Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation | JMA Journal

  https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2023-0038

  Takayasu arteritis (TAK) is a type of large-vessel vasculitis that predominantly affects young females. The precise pathomechanism of TAK is still under investigation. In TAK, the vasa vasorum is considered to be the initial inflammatory site. Disruption of the vasa vasorum induces the entry of inflammatory cells into the vascular wall of large vessels between the media and adventitia, and infiltrated cells damage the vascular components, eventually leading to stenosis or dilatation of the affected arteries. […] Although the roles of B cells in TAK are poorly understood, recent evidence supports their contribution to the pathogenicity of TAK. […] The initial inflammation of TAK begins around the vasa vasorum, which leads to the infiltration of inflammatory cells around the border of the media and adventitia.

• #5 Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation | JMA Journal

  https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2023-0038

  Infiltrating cells of aortic tissue samples from TAK consist of macrophages, CD4+ T cells, CD8+ T cells, T cells, and natural killer cells, and cell-mediated autoimmunity has been implicated in the pathogenesis of TAK. […] Therefore, failure of tolerance against the tissue around the vasa vasorum would be a critical pathogenesis in TAK, and the involvement of dendritic cells is also considered. […] Although granulomatous vasculitis is a typical pathological finding, T cells, including Th1 and Th17 cells, have been implicated as key players in systemic autoimmune responses. […] Myeloid cells, including macrophages, are effector cells that promote disease progression via several pathways. […] Inflammation results in fibrous thickening and scarring of the adventitia, which is more prominent in TAK than in GCA.

• #6 Clinical features and diagnosis of Takayasu arteritis – UpToDate

  https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print

  Takayasu arteritis (TAK) is classified as a large-vessel vasculitis because it primarily affects the aorta and its primary branches. […] The pathogenesis of Takayasu arteritis (TAK) is poorly understood. Cell-mediated mechanisms are thought to be of primary importance and may be similar to those in giant cell arteritis (GCA). […] Some studies have identified genetic links to disease susceptibility that may help explain differences in prevalence geographically and could lead to a deeper understanding of key underlying pathways of disease pathogenesis. […] Immunohistopathologic examination has shown that the infiltrating cells in aortic tissue mainly consist of cytotoxic lymphocytes, especially gamma delta T lymphocytes. […] These cells may cause vascular injury by releasing large amounts of the cytolytic protein perforin.

• #7 Takayasu’s arteritis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Takayasu’s_arteritis_pathophysiology

  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. […] 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. […] 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 T cells, T cells (CD4 and CD8), and natural killer cells play an important role in the vascular injury.

• #8 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  The cellular infiltrate in Takayasu arteritis contains about 15% each of CD4+ and CD8+ T cells. IL-6 is a proinflammatory cytokine mainly synthesized by activated monocytes, macrophages, and T cells. IL-6 activates B cells and enhances T-cell cytotoxicity, natural killer cell activity, fibroblast proliferation, and acute-phase protein synthesis. Amplification of proinflammatory cytokine genes from aortic tissue reveals strong expression of IL-6 transcripts. […] In a case report, M tuberculosis and its 65-kd heat shock protein was implicated in the etiology. Patients with Takayasu arteritis were found to have higher immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) titers against the M tuberculosis extract than did patients without the condition. […] One article reported the presence of CD3+ T cells and IgG antibodies reactive to circulating antimycobacterial heat shock protein 65 (mHSP65) antibodies and to its human homologue, hHSP60.

• #9

  https://link.springer.com/article/10.1007/s11926-020-00948-x

  Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are auto-inflammatory and autoimmune diseases with a highly selective tissue tropism for medium and large arteries. In both diseases, CD4+ T cells and macrophages form granulomatous lesions within the arterial wall, a tissue site normally protected by immune privilege. […] A significant difference lies in the composition of the wall-infiltrating immune cell compartment, which in TAK includes a significant population of CD8+ T cells as well as natural killer cells, specifying disparate disease effector pathways mediating tissue damage and vessel wall remodeling. […] Despite the similarities in tissue tropism and histomorphology, GCA and TAK are two distinct vasculitides that rely on separate disease mechanisms and require disease-specific approaches in diagnosis and management. […] This study has identified endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) as autoantigens on endothelial cells in patients with Takayasu arteritis. Bound autoantibodies promote inflammation by blocking the negative regulatory role of the two receptors.

• #10 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  The cellular infiltrate in Takayasu arteritis contains about 15% each of CD4+ and CD8+ T cells. IL-6 is a proinflammatory cytokine mainly synthesized by activated monocytes, macrophages, and T cells. IL-6 activates B cells and enhances T-cell cytotoxicity, natural killer cell activity, fibroblast proliferation, and acute-phase protein synthesis. Amplification of proinflammatory cytokine genes from aortic tissue reveals strong expression of IL-6 transcripts. […] In a case report, M tuberculosis and its 65-kd heat shock protein was implicated in the etiology. Patients with Takayasu arteritis were found to have higher immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) titers against the M tuberculosis extract than did patients without the condition. […] One article reported the presence of CD3+ T cells and IgG antibodies reactive to circulating antimycobacterial heat shock protein 65 (mHSP65) antibodies and to its human homologue, hHSP60.

• #11 The critical role of IL-6 in the pathogenesis of Takayasu arteritis

  https://www.clinexprheumatol.org/abstract.asp?a=9409

  Significantly increased levels of IL-6 were detected in peripheral blood and aortic tissues of untreated patients. IL-6 might be a sensitive biomarker to assess disease activity and could be critical in the immunopathogenesis of TAK.

• #12 The critical role of IL-6 in the pathogenesis of Takayasu arteritis

  https://www.clinexprheumatol.org/abstract.asp?a=9409

  Significantly increased levels of IL-6 were detected in peripheral blood and aortic tissues of untreated patients. IL-6 might be a sensitive biomarker to assess disease activity and could be critical in the immunopathogenesis of TAK.

• #13 Fellow’s Forum Case Report: Takayasu’s Arteritis – Page 7 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/fellows-forum-case-report-takayasus-arteritis/7/?singlepage=1

  Takayasus arteritis (TAK) is a well-established but rare form of large-vessel vasculitis. […] It is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Inflammation leads to thickening of the arterial wall, resulting in occlusion, stenosis, dilatation and thrombus formation. […] The granulomatous nature of inflammation in Takayasus arteritis suggests a potential role of tumor necrosis factor-alpha in disease pathogenesis. […] The mainstay of therapy is suppression of inflammation and preservation of vascular competence. Initial treatment is typically glucocorticoids at a dose of 1 mg/kg/day. […] Although immunosuppressant therapy may treat inflammation and prevent new vascular lesions, surgical or endovascular interventions are sometimes required to treat chronic, severe vascular complications.

• #14 Management of cardiac manifestations in Takayasu arteritis

  https://www.oaepublish.com/articles/2574-1209.2020.15

  Takayasu arteritis (TA) is a chronic vasculitis involving large vessels. It mainly involves the aorta and its branches, pulmonary artery and coronary artery. Though the cause of TA is unclear, there is a strong association with genetic predisposition, environmental factors and role of microbes. The arterial wall hosts the pathogenic activated T lymphocytes and macrophages leading to granulomatous inflammation and ultimately vessel wall damage. Proinflammatory cytokines, namely interleukin-6 (IL-6) and tumor necrosis factor- (TNF-), are elevated in TA, which correlates with disease activity. […] Active inflammation leads to intimal proliferation and fibrous contraction in the region around the coronary ostium leading to the narrowing of the coronary artery. Ischemia is one of the major causes of death in TA patients. Though extremely difficult, a high degree of suspicion is necessary to diagnosis these patients in the pre-stenotic phase. In patients with diminished/absent pulse, it may take several months/years, before the coronary artery becomes involved.

• #15 Takayasu’s arteritis associated with eosinophilic gastroenteritis, possibly via the overactivation of Th17 | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-018-0251-z

  Takayasus arteritis (TA) is a large-vessel vasculitis pathologically characterized by granulomatous necrotizing vasculitis with giant cells. Although the cause of TA is still unclear, genetic factors as well as immunological abnormalities, particularly the overactivation of Th1 and Th-17, are considered to play important roles in the pathogenesis of this disease. […] In this case, the expression of IL-17 mRNA in the colon mucosa greatly decreased after prednisolone treatment for EGE. […] This is the first report of TA complicated with EGE, and the overactivation of TH17 is considered to be associated with the pathogenesis of these two diseases. […] From immunological perspectives, TH1 and TH17 immunity is thought to be important in driving TA-related inflammation, both systemically and in blood vessels. High levels of TH1 cytokines, such as IL-1, IL-2, IL-6, IL-12, TNF- and IFN-, and TH17 cytokines such as IL-17A are associated with disease activity.

• #16 Takayasu’s arteritis associated with eosinophilic gastroenteritis, possibly via the overactivation of Th17 | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-018-0251-z

  Takayasus arteritis (TA) is a large-vessel vasculitis pathologically characterized by granulomatous necrotizing vasculitis with giant cells. Although the cause of TA is still unclear, genetic factors as well as immunological abnormalities, particularly the overactivation of Th1 and Th-17, are considered to play important roles in the pathogenesis of this disease. […] In this case, the expression of IL-17 mRNA in the colon mucosa greatly decreased after prednisolone treatment for EGE. […] This is the first report of TA complicated with EGE, and the overactivation of TH17 is considered to be associated with the pathogenesis of these two diseases. […] From immunological perspectives, TH1 and TH17 immunity is thought to be important in driving TA-related inflammation, both systemically and in blood vessels. High levels of TH1 cytokines, such as IL-1, IL-2, IL-6, IL-12, TNF- and IFN-, and TH17 cytokines such as IL-17A are associated with disease activity.

• #17 Journal of APPLIED BIOMEDICINE: Takayasu arteritis – epidemiology, pathogenesis, diagnosis and treatment

  https://jab.zsf.jcu.cz/artkey/jab-201901-0002_takayasu-arteritis-epidemiology-pathogenesis-diagnosis-and-treatment.php

  Takayasu disease belongs to the group of autoimmune vasculitis which most often affects the aorta and its branches. […] Pathogenesis of Takayasu’s arteritis: a 2011 update. […] Th1 and Th17 cytokines drive inflammation in Takayasu arteritis. […] Immunopathogenesis of Takayasu arteritis. […] Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis.

• #18 Pathogenesis of Takayasu’s arteritis: A 2011 update

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2026879782

  Th1 lymphocytes drive the formation of giant cells through the production of interferon-, and activate macrophages with release of VEGF resulting in increased neovascularisation and PDGF, resulting in smooth muscle migration and intimal proliferation. […] Th17 cells induced by the IL-23 microenvironnement also contribute to vascular lesions through activation of infiltrating neutrophils. […] Although still controversial, dendritic cells may cooperate with B lymphocytes and trigger the production of anti-endothelial cell auto-antibodies resulting in complement-dependent cytotoxicity against endothelial cells. […] In a near future, novel drugs specifically designed to target some of the pathogenic mechanisms described above could be expanding the physician’s therapeutic arsenal in Takayasu’s arteritis.

• #19 Pathophysiology, Diagnosis, and Management of Takayasu Arteritis: A Review of Current Advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10386905/

  Takayasu arteritis (TA) is characterized by autoimmune-mediated inflammation, vascular remodeling, and endothelial dysfunction. […] The pathogenesis of TA involves a combination of genetic and immune-mediated factors. […] The immune system plays a significant role in the pathogenesis of TA, involving both adaptive and innate immune responses. […] Autoimmunity, particularly B cell-mediated autoimmunity, is implicated in TA. […] The activation of inflammatory M1 macrophages and reparative M2 macrophages is one potential mechanism underlying vascular fibrosis in TA. […] The mammalian target organ of rapamycin complex 1 (mTORC1) activation and Notch-1 signaling are the key mechanisms driving the activation of Th1 and Th17 lymphocytes in the inflamed arterial wall of TA. […] IL-6, a proinflammatory cytokine, plays a dual role in TA by driving vascular inflammation and fibrosis.

• #20 Pathogenesis of Takayasu’s arteritis: A 2011 update

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2026879782

  Th1 lymphocytes drive the formation of giant cells through the production of interferon-, and activate macrophages with release of VEGF resulting in increased neovascularisation and PDGF, resulting in smooth muscle migration and intimal proliferation. […] Th17 cells induced by the IL-23 microenvironnement also contribute to vascular lesions through activation of infiltrating neutrophils. […] Although still controversial, dendritic cells may cooperate with B lymphocytes and trigger the production of anti-endothelial cell auto-antibodies resulting in complement-dependent cytotoxicity against endothelial cells. […] In a near future, novel drugs specifically designed to target some of the pathogenic mechanisms described above could be expanding the physician’s therapeutic arsenal in Takayasu’s arteritis.

• #21 Giant Cell Arteritis versus Takayasu Arteritis: An Update | MJR – Mediterranean Journal of Rheumatology

  http://www.mjrheum.org/june-2020/newsid792/240/showfulltext792/1

  A very interesting finding is that in patients with GCA who are treated with glucocorticoids (GCs), the level of circulating Th-17 cytokines is significantly reduced after the treatment, whereas the level of Th-1 cytokines is unaffected in patients with chronic disease. The same statement stands even for the cellular populations of Th17 and Th1 cells in specimens of temporal artery biopsies (TABs) from patients with GCA. On the contrary, in TAK, the level of Th1-related cytokines is reduced after the treatment, whereas the level of Th-17 cytokines is unaffected.

• #22 Insights into Pathogenesis of Takayasu’s Arteritis

  https://www.longdom.org/open-access/insights-into-pathogenesis-of-takayasus-arteritis-6276.html

  The T-cell dominated perspective of TA has recently been challenged. New evidence supports an important role for B-cells. […] Management of Takayasu’s disease remains a challenge because of an incomplete understanding of pathogenesis, lack of reliable biomarkers of disease activity and limited treatment options. However, recent insights into pathogenesis, an improved understanding of target selectivity and emerging data on the use of biologic agents holds the promise of change for the better.

• #23 A Glimpse into Humoral Response and Related Therapeutic Approaches of Takayasu’s Arteritis

  https://www.mdpi.com/1422-0067/25/12/6528

  Takayasu’s arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing body of evidence bears testimony to the widespread effects of B cells on disease pathogenesis and progression. […] Distinct alterations in peripheral B cell subsets have been described in individuals with TAK. […] Moreover, emerging data suggest that dysregulated signaling cascades downstream of B cell receptor families, including interactions with innate pattern recognition receptors such as toll-like receptors, as well as co-stimulatory molecules like CD40, CD80 and CD86, may result in the selection and proliferation of autoreactive B cell clones in TAK.

• #24 Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis | Nature Communications

  https://www.nature.com/articles/s41467-020-15088-0

  The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. […] In mechanistic studies, EPCR and SR-BI function as negative regulators of endothelial activation. […] Autoantibodies against EPCR and SR-BI block the functions of their targets, thereby promoting pro-inflammatory phenotype. […] Granulomatous vasculitis is a typical pathological finding, and T cells have been implicated as key players; myeloid cells, including macrophages, are effector cells that promote disease progression. […] Several studies identified the pathogenic effects of AECAs in TAK, including endothelial cell activation, cytotoxicity, cytokine production, and apoptosis. […] EPCR has also an effect on human T cells and impair Th17 differentiation.

• #25 Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation | JMA Journal

  https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2023-0038

  The pathogenic potential of the identified Abs was also investigated. Both EPCR and SR-BI are expressed on the endothelium in the vasa vasorum, as well as in the intima of the aorta. […] Interestingly, both EPCR and SR-BI suppress endothelial activation after an inflammatory stimulus. Abs against EPCR and SR-BI block the function of the corresponding ligands, thus inhibiting the resolution of endothelial activation, which has the potential to maintain vascular inflammation. […] These results indicate that Abs identified in TAK contribute to its pathophysiology in many ways. […] In addition to previous knowledge regarding the roles of T cells and myeloid cells in TAK, investigation of the interaction between dysbiosis and dysregulation of B cells and Abs is required for a comprehensive understanding of the complex pathophysiology of TAK.

• #26 Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis | Nature Communications

  https://www.nature.com/articles/s41467-020-15088-0

  The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. […] In mechanistic studies, EPCR and SR-BI function as negative regulators of endothelial activation. […] Autoantibodies against EPCR and SR-BI block the functions of their targets, thereby promoting pro-inflammatory phenotype. […] Granulomatous vasculitis is a typical pathological finding, and T cells have been implicated as key players; myeloid cells, including macrophages, are effector cells that promote disease progression. […] Several studies identified the pathogenic effects of AECAs in TAK, including endothelial cell activation, cytotoxicity, cytokine production, and apoptosis. […] EPCR has also an effect on human T cells and impair Th17 differentiation.

• #27 Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis | Nature Communications

  https://www.nature.com/articles/s41467-020-15088-0

  Anti-EPCR autoantibodies blocked the negative effect of APC on Th17 differentiation, thus promoting this differentiation. […] Because the autoantigens identified were plasma membrane protein receptors, they had the potential to either block or stimulate receptor signaling. […] We showed that anti-EPCR and anti-SR-BI autoantibodies functioned as blocking antibodies. […] The mechanisms how they are regulated in vascular inflammation should also be investigated in future.

• #28 Pathogenesis of Takayasu’s arteritis: A 2011 update

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2026879782

  While our knowledge of the pathogenesis of Takayasu’s arteritis (TA) has considerably improved during the last decade, the exact pathogenic sequence remains to be elucidated. […] It is now hypothesised that an unknown stimulus triggers the expression of the 65 kDa Heat-shock protein in the aortic tissue which, in turn, induces the Major Histocompatibility Class I Chain-Related A (MICA) on vascular cells. […] The T cells and NK cells expressing NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. […] Pro-inflammatory cytokines are released and increase the recruitment of mononuclear cells within the vascular wall. […] T cells infiltrate and recognize one or a few antigens presented by a shared epitope, which is associated with specific major Histocompatibility Complex alleles on the dendritic cells, these latter being activated through Toll-like receptors.

• #29 Giant Cell Arteritis versus Takayasu Arteritis: An Update | MJR – Mediterranean Journal of Rheumatology

  http://www.mjrheum.org/june-2020/newsid792/240/showfulltext792/1

  The pathogenesis of TAK is poorly understood. Similarly to GCA, there is an inflammatory cascade initiated by impaired DCs and orchestrated by Th-1 and Th-17 responses resulting in the granulomatous infiltrate. However, there are some differences between GCA and TAK. In TAK, a currently unknown stimulus causes the overexpression of heat shock protein 65 kDA (HSP-65) which causes, in turn, the expression of cell surface protein MICA on vascular cells. MICA functions as a ligand for the NKG2D receptor, a receptor which is usually expressed in T-cells, CD8- T-cells and NK-cells. The recognition of MICA by T-cells and NK-cells results in the production of perforin with subsequent vascular inflammation and damage. The dysregulated immune response and the uncontrolled activation of repair mechanisms contribute to the vascular damage seen in TAK.

• #30 Pathogenesis of Takayasu’s arteritis: A 2011 update

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2026879782

  While our knowledge of the pathogenesis of Takayasu’s arteritis (TA) has considerably improved during the last decade, the exact pathogenic sequence remains to be elucidated. […] It is now hypothesised that an unknown stimulus triggers the expression of the 65 kDa Heat-shock protein in the aortic tissue which, in turn, induces the Major Histocompatibility Class I Chain-Related A (MICA) on vascular cells. […] The T cells and NK cells expressing NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. […] Pro-inflammatory cytokines are released and increase the recruitment of mononuclear cells within the vascular wall. […] T cells infiltrate and recognize one or a few antigens presented by a shared epitope, which is associated with specific major Histocompatibility Complex alleles on the dendritic cells, these latter being activated through Toll-like receptors.

• #31 New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory

  https://www.mdpi.com/2076-0817/7/3/73

  In support of this assumption is the fact that an increased expression of 65 kDa HSP has been consistently found in aortic tissues of TAK patients, and specific T-cells and autoantibodies recognizing both human 60 kDa HSP and 65 kDa HSP have been observed in TAK patients. […] The elevated levels of cytokines detected in patients with TAK, may reflect the presence of an inflammatory process, regardless the triggering mechanism, however the release of certain cytokines may reflect the immune response against latent or active microbe infection. […] An association of microorganisms with TAK has been extensively investigated and, so far, based on epidemiological and laboratory data, the most likely pathogen that appears to be implicated in the pathogenesis of TAK is mTB. […] It is expected that ongoing studies investigating the gut microbiome composition in patients with TAK will likely shed some light on a putative implication of microbes with the pathogenesis of this disease.

• #32 Takayasu’s arteritis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Takayasu’s_arteritis_pathophysiology

  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. […] 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. […] 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 T cells, T cells (CD4 and CD8), and natural killer cells play an important role in the vascular injury.

• #33 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  The genetic susceptibility factor that has been most consistently associated with Takayasu arteritis is the human leukocyte antigen (HLA) allele HLA-B*52, which has been confirmed in several ethnicities. HLA-B*52 has a higher prevalence in Asians, which may help explain the greater frequency of Takayasu arteritis in this population. […] Carriage of HLA-B52 is associated with more severe disease, with a higher incidence of left ventricular wall abnormalities and aortic regurgitation, and earlier disease onset. […] Other HLA alleles have also been implicated; for example, HLA-B39, HLA-DRB11502, and HLA-DRB10405 have also been associated with the disease in Japanese patients. HLA-B*39 is associated with renal artery stenosis. […] In addition, genome-wide association studies have identified several non-HLA susceptibility loci. […] One study demonstrated an association between several cases of Takayasu arteritis and CD36 deficiency (CD36d).

• #34 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  The genetic susceptibility factor that has been most consistently associated with Takayasu arteritis is the human leukocyte antigen (HLA) allele HLA-B*52, which has been confirmed in several ethnicities. HLA-B*52 has a higher prevalence in Asians, which may help explain the greater frequency of Takayasu arteritis in this population. […] Carriage of HLA-B52 is associated with more severe disease, with a higher incidence of left ventricular wall abnormalities and aortic regurgitation, and earlier disease onset. […] Other HLA alleles have also been implicated; for example, HLA-B39, HLA-DRB11502, and HLA-DRB10405 have also been associated with the disease in Japanese patients. HLA-B*39 is associated with renal artery stenosis. […] In addition, genome-wide association studies have identified several non-HLA susceptibility loci. […] One study demonstrated an association between several cases of Takayasu arteritis and CD36 deficiency (CD36d).

• #35 Takayasu’s arteritis – Wikipedia

  https://en.wikipedia.org/wiki/Takayasu%27s_arteritis

  A recent genome-wide association study (GWAS) identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and the intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)).

• #36 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  Congestive heart failure is a common finding, much more so than dilated cardiomyopathy, myocarditis, and pericarditis, which also have been reported. In patients with pulmonary artery involvement, the right artery appears to be affected more than the left, Complications of pulmonary artery involvement include pneumonia, interstitial pulmonary fibrosis, and alveolar damage. […] Other pathophysiologic consequences include hypotensive ischemic retinopathy, vertebrobasilar ischemia, microaneurysms, carotid stenosis, hypertensive encephalopathy, and inflammatory bowel disease. Rarely, Takayasu arteritis has also been associated with glomerulonephritis, systemic lupus erythematosus, polymyositis, polymyalgia rheumatica, rheumatoid arthritis, Still disease, and ankylosing spondylitis. […] The underlying pathologic process is inflammatory, with several etiologic factors having been proposed, including infection with spirochetes, Mycobacterium tuberculosis, and streptococcal organisms; and circulating antibodies due to an autoimmune process. Genetic susceptibility factors have been identified.

• #37 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  The cellular infiltrate in Takayasu arteritis contains about 15% each of CD4+ and CD8+ T cells. IL-6 is a proinflammatory cytokine mainly synthesized by activated monocytes, macrophages, and T cells. IL-6 activates B cells and enhances T-cell cytotoxicity, natural killer cell activity, fibroblast proliferation, and acute-phase protein synthesis. Amplification of proinflammatory cytokine genes from aortic tissue reveals strong expression of IL-6 transcripts. […] In a case report, M tuberculosis and its 65-kd heat shock protein was implicated in the etiology. Patients with Takayasu arteritis were found to have higher immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) titers against the M tuberculosis extract than did patients without the condition. […] One article reported the presence of CD3+ T cells and IgG antibodies reactive to circulating antimycobacterial heat shock protein 65 (mHSP65) antibodies and to its human homologue, hHSP60.

• #38 New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory

  https://www.mdpi.com/2076-0817/7/3/73

  Although the pathogenesis of TAK is not entirely known, the cause of this disease is likely rooted in a persistent inflammatory response from a genetically prone individual. […] An immune reaction against antigens, likely derived from microorganisms, either commensals or pathogens, is believed to be the initial event. […] Granuloma formation and tissue fibrosis result from the persistent activation of immune cells and the prolonged release of proinflammatory cytokines. […] The persistent activation of other immune cells, including Th17 and NK cells can also promote granuloma formation and fibrosis via the release of cytokines. […] Furthermore, the possibility that specific immune response against microbe proteins cross-react with structurally related proteins of the host (molecular mimicry) has been proposed as the most plausible triggering mechanism.

• #39 Specific microbiome profile in Takayasu’s arteritis and giant cell arteritis | Scientific Reports

  https://www.nature.com/articles/s41598-021-84725-5

  Recent studies have provided evidence of a close link between specific microbiota and inflammatory disorders. […] The pathogenesis of LVV is not well understood. LVV are characterized by an inflammatory infiltrate located in the arterial wall, but the mechanisms leading to such lesions remain unclear. […] Specific toll-like receptors (TLR) involved in pathogen-associated molecular pattern recognition have also been shown to be involved in LVV pathogenesis. […] The close relationship between gut dysbiosis and altered immune response has been well established in recent studies and such alterations may be involved, at least in part, in the pathogenesis of autoimmune diseases. […] Emerging data reporting the presence of a specific microbiome in the arteries and blood of patients with large-vessel vasculitis suggest that different communities of microbes may drive the inflammatory process in vasculitis.

• #40 Specific microbiome profile in Takayasu’s arteritis and giant cell arteritis | Scientific Reports

  https://www.nature.com/articles/s41598-021-84725-5

  We found for the first time specific alterations of the blood microbiome in LVV patients compared with healthy donors, and between LVV types (i.e. TAK compared with GCA). These alterations were associated with enrichment of specific metabolic pathways, which may be involved in LVV pathogenesis. […] We can speculate that some bacteria or bacterial products, such as bacterial DNA, may translocate from the gut or other mucous membranes (mouth) and then interact with the immune system present within the vascular wall, leading to activation of the immune process and thus participation in LVV pathogenesis. […] We observed an enrichment in the bacterial porphyrin and chlorophyll pathways in TAK patients. […] These results highlight the close link between the microbiome, metabolomic changes and inflammation.

• #41 Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation | JMA Journal

  https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2023-0038

  Takayasu arteritis (TAK) is a type of large-vessel vasculitis that predominantly affects young females. The precise pathomechanism of TAK is still under investigation. In TAK, the vasa vasorum is considered to be the initial inflammatory site. Disruption of the vasa vasorum induces the entry of inflammatory cells into the vascular wall of large vessels between the media and adventitia, and infiltrated cells damage the vascular components, eventually leading to stenosis or dilatation of the affected arteries. […] Although the roles of B cells in TAK are poorly understood, recent evidence supports their contribution to the pathogenicity of TAK. […] The initial inflammation of TAK begins around the vasa vasorum, which leads to the infiltration of inflammatory cells around the border of the media and adventitia.

• #42 Role of inflammatory markers in Takayasu arteritis disease monitoring | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-14-62

  Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis that can result in significant morbidity and mortality secondary to progressive stenosis and occlusion. […] The evolution of these symptoms is due to progressing vascular lesions secondary to inflammatory processes. […] However, relying on the inflammatory marker ESR to distinguish active from inactive TA yields only a 72% sensitivity and a 56% specificity predictor value. […] This patients clinical course supports the hypothesis that inflammatory markers alone may not be sufficient to track the progression of TA, and reaffirms the need to monitor disease progression with more extensive screening. […] The pathophysiology of this disease can be divided into early, intermediate and chronic stages. Early in the disease process, lymphocytes infiltrate the adventitia through activated vasa-vasorum endothelial cells. The lymphocytes are stimulated by circulating cytokines to produce matrix metalloproteinases (MMP), leading to the destruction of the elastic fibers in the arterial wall. Increased adventitial neovascularization and up-regulation of adhesion molecules results in increased recruitment of inflammatory cells. In the intermediate stage, there is secondary deposition of mucopolysaccharides and fibroblasts and smooth muscle cell proliferation, encouraged by TNF-alpha. Eventually the intima becomes hypertrophied due to fibrocellular thickening. The pathological changes occurring in all layers lead to the narrowing of the vascular lumen, which result in stenosis and occlusion. In the chronic phase, inflammatory lesions progress to scars and the vessels become fibrotic and calcified.

• #43 Role of inflammatory markers in Takayasu arteritis disease monitoring | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-14-62

  The spread of vascular lesions in TA is thought to develop systemically rather than from adjacent vascular beds. […] Despite their usage, neither ESR nor CRP can distinguish active from inactive disease with the necessary clinical accuracy. […] Relying on these inflammatory markers alone to monitor disease progression can have severe and even lethal consequences for patients. […] Therefore, ESR and CRP should be viewed in the context of the patients clinical course and imaging. […] The unreliability of ESR and CRP has prompted the search for a more reliable serological marker of disease activity. […] These serological markers show promise as future biomarkers for TA. […] This case suggests that inflammatory markers alone are not sufficient to monitor disease activity, highlighting the need for frequent follow up imaging.

• #44 Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation | JMA Journal

  https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2023-0038

  Infiltrating cells of aortic tissue samples from TAK consist of macrophages, CD4+ T cells, CD8+ T cells, T cells, and natural killer cells, and cell-mediated autoimmunity has been implicated in the pathogenesis of TAK. […] Therefore, failure of tolerance against the tissue around the vasa vasorum would be a critical pathogenesis in TAK, and the involvement of dendritic cells is also considered. […] Although granulomatous vasculitis is a typical pathological finding, T cells, including Th1 and Th17 cells, have been implicated as key players in systemic autoimmune responses. […] Myeloid cells, including macrophages, are effector cells that promote disease progression via several pathways. […] Inflammation results in fibrous thickening and scarring of the adventitia, which is more prominent in TAK than in GCA.

• #45 Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu’s arteritis | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/83/11/1522

  Objectives Arterial wall inflammation and remodelling are the characteristic features of Takayasus arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. […] The findings of this study indicate that premature vascular smooth muscle cells (VSMCs) senescence contributed substantially to vascular inflammation in patients with TAK by increasing secretion of senescence-associated proinflammatory factors. Furthermore, vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence in TAK. […] In conclusion, VSMCs senescence is present in patients with TAK, and contributes substantially to vascular inflammation. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence in TAK.

• #46 Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu’s arteritis | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/83/11/1522

  Objectives Arterial wall inflammation and remodelling are the characteristic features of Takayasus arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. […] The findings of this study indicate that premature vascular smooth muscle cells (VSMCs) senescence contributed substantially to vascular inflammation in patients with TAK by increasing secretion of senescence-associated proinflammatory factors. Furthermore, vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence in TAK. […] In conclusion, VSMCs senescence is present in patients with TAK, and contributes substantially to vascular inflammation. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence in TAK.

• #47 Takayasu Arteritis – Musculoskeletal and Connective Tissue Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/vasculitis/takayasu-arteritis

  The diagnosis of Takayasu arteritis is suspected when symptoms suggest ischemia of organs supplied by the aorta or its branches or when peripheral pulses are decreased or absent in patients at low risk of atherosclerosis and other aortic disorders, especially in young females. […] Characteristic findings include stenosis, occlusion, irregularities in arterial lumens, poststenotic dilation, collateral arteries around obstructed vessels, and aneurysms. […] Takayasu arteritis can progress silently even when clinical and laboratory studies suggest complete remission. Therefore, periodic imaging of the aorta and large arteries is mandatory. […] Corticosteroids are the cornerstone of Takayasu arteritis treatment. A second immunosuppressant is frequently considered at onset of treatment with corticosteroid, especially in severe cases.

• #48 Takayasu Disease and Stroke

  https://practicalneurology.com/articles/2020-jan/takayasu-disease-and-stroke

  The absence of elevated inflammatory markers does not exclude the diagnosis of TA and changes in their levels cannot be used to monitor responses to therapy. […] Information about the status of the arterial wall, including gadolinium enhancement suggestive of inflammation, and the development of both extracranial and intracranial vascular lesions can be achieved with MRI and magnetic resonance angiography (MRA). […] The combination of CT and positron emission tomography (PET) may be used to assess vascular wall inflammation, although this combination is costly and involves large radiation exposure. […] A major relapse is defined as new ischemic symptoms or progressive inflammatory changes. […] Although an increase in inflammatory markers may prompt new vascular imaging, the changes should not, on their own, result in new treatment unless new ischemic symptoms are also present. […] Several biologic antirheumatologic agents show promise as disease-modifying treatments. […] There is some evidence that the TNF- inhibitors and interleukin-6 antagonists are effective in the treatment of TA.

• #49 New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory

  https://www.mdpi.com/2076-0817/7/3/73

  Takayasu arteritis (TAK) is a chronic vasculitis that mainly affects the aorta, its major branches, and the pulmonary arteries. […] Nevertheless, while it is well-known that TAK is associated with a profound inflammatory process, possibly rooted to an autoimmune disorder, its precise etiology has remained largely unknown. […] In addition, novel biological and immunomodulatory agents, such as anti-TNF agents and tocilizumab, a monoclonal antibody against interleukin 6 receptor, have shown promising therapeutic potential in patients with TAK. […] It is currently unknown if the presence of pathogenic microbes in the vascular tissues has a role in the development of TAK or if dysbiosis of the gut is implicated in the pathogenesis of this disease. […] The inflammatory process typically involves the inner wall and spares the outside of the blood vessels, progressing from a granulomatous inflammation (with infiltrating monocytes and lymphocytes) in early stages of the disease, to a less obvious inflammatory reaction in advances stages of the disease characterized by adventitial fibrosis, smooth muscle proliferation in the arterial intima and ultimately arterial stenosis.

• #50 A Glimpse into Humoral Response and Related Therapeutic Approaches of Takayasu’s Arteritis

  https://www.mdpi.com/1422-0067/25/12/6528

  Despite the importance of the humoral immune response, a systematic understanding of how autoreactive B cells contribute to the pathogenic process is still lacking. This review provides a comprehensive overview of the biological significance of B cell-mediated autoimmunity in TAK pathogenesis, as well as insights into therapeutic strategies targeting the humoral response. […] We believe that further identification of the pathogenic role of autoimmune B cells and the underlying regulation system will lead to deeper personalized management of TAK patients.

• #51 Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu’s arteritis | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/83/11/1522

  Objectives Arterial wall inflammation and remodelling are the characteristic features of Takayasus arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. […] The findings of this study indicate that premature vascular smooth muscle cells (VSMCs) senescence contributed substantially to vascular inflammation in patients with TAK by increasing secretion of senescence-associated proinflammatory factors. Furthermore, vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence in TAK. […] In conclusion, VSMCs senescence is present in patients with TAK, and contributes substantially to vascular inflammation. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence in TAK.

• #52 Takayasu Arteritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459127/

  Takayasu arteritis, aka pulseless disease, is a systemic inflammatory condition which leads to damage of the medium and large arteries and their branches. […] An abnormality in cell-mediated immunity seems to be its main pathogenesis, but its etiology is still largely unknown. […] At its core it is characterized as an inflammatory granulomatous vasculitis of medium and large arteries, which leads to transmural fibrous thickening of the arterial walls, leading to multiple vascular obstructions and eventual ischemic changes. […] Cell-mediated immunity involving CD4+ and CD8+ T cells may play a key role in the pathophysiology of Takayasu arteritis, as these cells support the formation of granulomas and potentially activate the activities of various proteases such as matrix metalloproteinase (MMP), as well as other cells which promote chronic inflammation and fibrosis formation. […] There continues to be a substantial lack of understanding of the pathogenesis of Takayasu arteritis, and the etiology is largely unknown.

• #53

  https://link.springer.com/article/10.1007/s11926-020-00948-x

  Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are auto-inflammatory and autoimmune diseases with a highly selective tissue tropism for medium and large arteries. In both diseases, CD4+ T cells and macrophages form granulomatous lesions within the arterial wall, a tissue site normally protected by immune privilege. […] A significant difference lies in the composition of the wall-infiltrating immune cell compartment, which in TAK includes a significant population of CD8+ T cells as well as natural killer cells, specifying disparate disease effector pathways mediating tissue damage and vessel wall remodeling. […] Despite the similarities in tissue tropism and histomorphology, GCA and TAK are two distinct vasculitides that rely on separate disease mechanisms and require disease-specific approaches in diagnosis and management. […] This study has identified endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) as autoantigens on endothelial cells in patients with Takayasu arteritis. Bound autoantibodies promote inflammation by blocking the negative regulatory role of the two receptors.

• #54 The critical role of IL-6 in the pathogenesis of Takayasu arteritis

  https://www.clinexprheumatol.org/abstract.asp?a=9409

  Significantly increased levels of IL-6 were detected in peripheral blood and aortic tissues of untreated patients. IL-6 might be a sensitive biomarker to assess disease activity and could be critical in the immunopathogenesis of TAK.

• #55 Management of cardiac manifestations in Takayasu arteritis

  https://www.oaepublish.com/articles/2574-1209.2020.15

  Takayasu arteritis (TA) is a chronic vasculitis involving large vessels. It mainly involves the aorta and its branches, pulmonary artery and coronary artery. Though the cause of TA is unclear, there is a strong association with genetic predisposition, environmental factors and role of microbes. The arterial wall hosts the pathogenic activated T lymphocytes and macrophages leading to granulomatous inflammation and ultimately vessel wall damage. Proinflammatory cytokines, namely interleukin-6 (IL-6) and tumor necrosis factor- (TNF-), are elevated in TA, which correlates with disease activity. […] Active inflammation leads to intimal proliferation and fibrous contraction in the region around the coronary ostium leading to the narrowing of the coronary artery. Ischemia is one of the major causes of death in TA patients. Though extremely difficult, a high degree of suspicion is necessary to diagnosis these patients in the pre-stenotic phase. In patients with diminished/absent pulse, it may take several months/years, before the coronary artery becomes involved.

• #56 Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis | Nature Communications

  https://www.nature.com/articles/s41467-020-15088-0

  The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. […] In mechanistic studies, EPCR and SR-BI function as negative regulators of endothelial activation. […] Autoantibodies against EPCR and SR-BI block the functions of their targets, thereby promoting pro-inflammatory phenotype. […] Granulomatous vasculitis is a typical pathological finding, and T cells have been implicated as key players; myeloid cells, including macrophages, are effector cells that promote disease progression. […] Several studies identified the pathogenic effects of AECAs in TAK, including endothelial cell activation, cytotoxicity, cytokine production, and apoptosis. […] EPCR has also an effect on human T cells and impair Th17 differentiation.

• #57 Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation | JMA Journal

  https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2023-0038

  The pathogenic potential of the identified Abs was also investigated. Both EPCR and SR-BI are expressed on the endothelium in the vasa vasorum, as well as in the intima of the aorta. […] Interestingly, both EPCR and SR-BI suppress endothelial activation after an inflammatory stimulus. Abs against EPCR and SR-BI block the function of the corresponding ligands, thus inhibiting the resolution of endothelial activation, which has the potential to maintain vascular inflammation. […] These results indicate that Abs identified in TAK contribute to its pathophysiology in many ways. […] In addition to previous knowledge regarding the roles of T cells and myeloid cells in TAK, investigation of the interaction between dysbiosis and dysregulation of B cells and Abs is required for a comprehensive understanding of the complex pathophysiology of TAK.

• #58 Pathogenesis of Takayasu’s arteritis: A 2011 update

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2026879782

  While our knowledge of the pathogenesis of Takayasu’s arteritis (TA) has considerably improved during the last decade, the exact pathogenic sequence remains to be elucidated. […] It is now hypothesised that an unknown stimulus triggers the expression of the 65 kDa Heat-shock protein in the aortic tissue which, in turn, induces the Major Histocompatibility Class I Chain-Related A (MICA) on vascular cells. […] The T cells and NK cells expressing NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. […] Pro-inflammatory cytokines are released and increase the recruitment of mononuclear cells within the vascular wall. […] T cells infiltrate and recognize one or a few antigens presented by a shared epitope, which is associated with specific major Histocompatibility Complex alleles on the dendritic cells, these latter being activated through Toll-like receptors.

• #59 Giant Cell Arteritis versus Takayasu Arteritis: An Update | MJR – Mediterranean Journal of Rheumatology

  http://www.mjrheum.org/june-2020/newsid792/240/showfulltext792/1

  The pathogenesis of TAK is poorly understood. Similarly to GCA, there is an inflammatory cascade initiated by impaired DCs and orchestrated by Th-1 and Th-17 responses resulting in the granulomatous infiltrate. However, there are some differences between GCA and TAK. In TAK, a currently unknown stimulus causes the overexpression of heat shock protein 65 kDA (HSP-65) which causes, in turn, the expression of cell surface protein MICA on vascular cells. MICA functions as a ligand for the NKG2D receptor, a receptor which is usually expressed in T-cells, CD8- T-cells and NK-cells. The recognition of MICA by T-cells and NK-cells results in the production of perforin with subsequent vascular inflammation and damage. The dysregulated immune response and the uncontrolled activation of repair mechanisms contribute to the vascular damage seen in TAK.

• #60 Takayasu Arteritis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/332378-overview

  The genetic susceptibility factor that has been most consistently associated with Takayasu arteritis is the human leukocyte antigen (HLA) allele HLA-B*52, which has been confirmed in several ethnicities. HLA-B*52 has a higher prevalence in Asians, which may help explain the greater frequency of Takayasu arteritis in this population. […] Carriage of HLA-B52 is associated with more severe disease, with a higher incidence of left ventricular wall abnormalities and aortic regurgitation, and earlier disease onset. […] Other HLA alleles have also been implicated; for example, HLA-B39, HLA-DRB11502, and HLA-DRB10405 have also been associated with the disease in Japanese patients. HLA-B*39 is associated with renal artery stenosis. […] In addition, genome-wide association studies have identified several non-HLA susceptibility loci. […] One study demonstrated an association between several cases of Takayasu arteritis and CD36 deficiency (CD36d).

• #61 Specific microbiome profile in Takayasu’s arteritis and giant cell arteritis | Scientific Reports

  https://www.nature.com/articles/s41598-021-84725-5

  We found for the first time specific alterations of the blood microbiome in LVV patients compared with healthy donors, and between LVV types (i.e. TAK compared with GCA). These alterations were associated with enrichment of specific metabolic pathways, which may be involved in LVV pathogenesis. […] We can speculate that some bacteria or bacterial products, such as bacterial DNA, may translocate from the gut or other mucous membranes (mouth) and then interact with the immune system present within the vascular wall, leading to activation of the immune process and thus participation in LVV pathogenesis. […] We observed an enrichment in the bacterial porphyrin and chlorophyll pathways in TAK patients. […] These results highlight the close link between the microbiome, metabolomic changes and inflammation.

• #62 Pathogenesis of Takayasu’s arteritis: A 2011 update

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2026879782

  Th1 lymphocytes drive the formation of giant cells through the production of interferon-, and activate macrophages with release of VEGF resulting in increased neovascularisation and PDGF, resulting in smooth muscle migration and intimal proliferation. […] Th17 cells induced by the IL-23 microenvironnement also contribute to vascular lesions through activation of infiltrating neutrophils. […] Although still controversial, dendritic cells may cooperate with B lymphocytes and trigger the production of anti-endothelial cell auto-antibodies resulting in complement-dependent cytotoxicity against endothelial cells. […] In a near future, novel drugs specifically designed to target some of the pathogenic mechanisms described above could be expanding the physician’s therapeutic arsenal in Takayasu’s arteritis.

• #63 Insights into Pathogenesis of Takayasu’s Arteritis

  https://www.longdom.org/open-access/insights-into-pathogenesis-of-takayasus-arteritis-6276.html

  The T-cell dominated perspective of TA has recently been challenged. New evidence supports an important role for B-cells. […] Management of Takayasu’s disease remains a challenge because of an incomplete understanding of pathogenesis, lack of reliable biomarkers of disease activity and limited treatment options. However, recent insights into pathogenesis, an improved understanding of target selectivity and emerging data on the use of biologic agents holds the promise of change for the better.

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