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Arthritis und Rheuma 2010; 30(04): 193-198
DOI: 10.1055/s-0037-1618020
Vaskulitiden
Schattauer GmbH

Die Pathogenese der Großgefäßvaskulitiden

The pathogenesis of large vessel vasculitis
C. Dejaco
1   Medizinische Universität Graz, Univ. Klinik für Innere Medizin, Abteilung für Rheumatologie, Graz, Österreich
,
A. D. Wagner
2   Medizinische Hochschule Hannover, Abteilung für Nieren- und Hochdruckerkrankungen, Hannover
› Author Affiliations
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Publication History

Publication Date:
26 December 2017 (online)

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Zusammenfassung

Vaskulitiden der großen Gefäße, wie die Riesenzellarteriitis (RZA) und die Takayasu-Arteriitis sind durch zelluläre Infiltrate in vaskulären Läsionen und dem Fehlen von Autoantikörpern gekennzeichnet. Bei der RZA wird vermutet, dass die durch Bakterien und/oder Viren ausgelöste Reifung von dendritischen Zellen eine Störung der Immuntoleranz verursacht. In Folge werden CD4+-T-Zellen und Makrophagen rekrutiert, wodurch es zu einer Zerstörung glatter Muskelzellen und der Membrana elastica interna kommt. Die nachfolgenden Reparationsprozesse mit Intimahyperplasie führen zu einem zunehmenden Lumenverschluss der betroffenen Gefäße. Im Unterschied zur RZA sind bei der Takayasu-Arteriitis CD8+-T-Zellen die dominierende Zellpopulation. Neben der antigenvermittelten Aktivierung werden diese Zellen auch antigenunabhängig über natürliche Killer-Zell-Rezeptoren stimuliert und verursachen durch Sekretion von Perforin direkt eine Schädigung der Gefäßwand.

Summary

Large vessel vasculitides including giant cell arteritis (GCA) and Takayasu arteritis are characterised by cellular infiltrates in the vessel wall and the absence of autoantibodies. Infectious agents are considered to cause maturation of vascular dendritic cells leading to the breakdown of immune tolerance. Consequently, CD4+T-cells and macrophages are recruited to the vascular lesion leading to the destruction of smooth muscle cells and the internal elastic lamina. In response to the injury, the artery generates intimal hyperplasia leading to luminal occlusion and subsequent tissue ischemia. Inflammatory lesions of patients with Takayasu arteritis are dominated by CD8+ T-cell infiltrates. These T-cells are activated by antigen dependent and independent stimuli and they directly contribute to vessel wall damage by the secretion of perforin.

Schlüsselwörter

Vaskulitis - Arteriitis temporalis - Polymyalgia rheumatica

Keywords

Vasculitis - temporal arteritis - polymyalgia rheumatica
 

  • Literatur

  • 1 Calamia KT, Hunder GG. Giant cell arteritis (temporal arteritis) presenting as fever of undetermined origin. Arthritis Rheum 1981; 24: 1414-1418.
    CrossrefPubMedSearch in Google Scholar
  • 2 Cauhan SK, Singh M, Nityanand S. Reactivity of gamma/delta T cells to human 60-kd heat-shock protein and their cytotoxicity to aortic endothelial cells in Takayasu arteritis. Arthritis Rheum 2007; 56: 2798-2802.
    CrossrefPubMedSearch in Google Scholar
  • 3 Dejaco C, Duftner C, Calamia KT, Schirmer M. Meeting report: 13th International Conference on Behçet’s disease. Pörtschach am Wörthersee, Austria, May 24–27, 2008. J Rheumatol 2009; 36: 1312-1317.
    CrossrefPubMedSearch in Google Scholar
  • 4 Dejaco C, Seifert T, Duftner C. et al. Diagnose und Therapie neurologischer Manifestationen bei entzündlich-rheumatischen Erkrankungen. Z Rheumatol 2008; 67: 386-396.
    PubMedSearch in Google Scholar
  • 5 Dejaco C, Wipfler-Freißmuth E, Duftner C, Schirmer M. Möglichkeiten der Krankheitsaktivitätsmessung bei Vaskulitiden im klinischen Alltag. Aktuel Rheumatol 2009; 34: 180-185.
    Thieme ConnectSearch in Google Scholar
  • 6 Duftner C, Seiler R, Dejaco C. et al. Increasing evidence for immune-mediated processes and new therapeutic approaches in abdominal aortic aneurysms-a review. Ann N Y Acad Sci 2006; 1085: 331-338.
    CrossrefPubMedSearch in Google Scholar
  • 7 Duhaut P, Bosshard S, Calvet A. et al. Giant cell arteritis, Polymyalgia rheumatica, and viral hypotheses: a multicenter, prospective case-control study. Groupe de Recherche sur l'Artérite à Cellules Géantes. J Rheumatol 1999; 26: 361-369.
    Search in Google Scholar
  • 8 Gonzalez-Gay MA, Blanco R, Rodriguez-Valverde V. et al. Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment. Arthritis Rheum 1998; 41: 1497-1504.
    CrossrefPubMedSearch in Google Scholar
  • 9 Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol 2002; 55: 481-486.
    CrossrefPubMedSearch in Google Scholar
  • 10 Kaiser M, Younge B, Bjornsson J. et al. Formation of new vasa vasorum in vasculitis. Production of angiogenic cytokines by multinucleated giant cells. Am J Pathol 1999; 155: 765-774.
    CrossrefPubMedSearch in Google Scholar
  • 11 Kaiser M, Weyand CM, Bjornsson J, Goronzy JJ. Platelet-derived growth factor, intimal hyperplasia, and ischemic complications in giant cell arteritis. Arthritis Rheum 1998; 41: 623-633.
    CrossrefPubMedSearch in Google Scholar
  • 12 Kawasaki A, Purvin V. Giant cell arteritis: an updated Review. Acta Ophthalmol 2009; 87: 13-32.
    CrossrefPubMedSearch in Google Scholar
  • 13 Klein RG, Hunder GG, Stanson AW, Sheps SG. Large artery involvement in giant cell (temporal) arteritis. Ann Intern Med 1975; 83: 806-812.
    CrossrefPubMedSearch in Google Scholar
  • 14 Labarrere CA, Zaloga GP. C-reactive protein: from innocent bystander to pivotal mediator of atherosclerosis. Am J Med 2004; 117: 499-507.
    CrossrefPubMedSearch in Google Scholar
  • 15 Lamprecht P. New pathogenetic aspects in primary systemic vasculitides. Internist 2009; 50: 291-297.
    CrossrefPubMedSearch in Google Scholar
  • 16 Lee GR. The anemia of chronic disease. Semin Hematol 1983; 20: 61-80.
    PubMedSearch in Google Scholar
  • 17 Ma-Krupa W, Jeon MS, Spoerl S. et al. Activation of arterial wall dendritic cells and breakdown of selftolerance in giant cell arteritis. J Exp Med 2004; 199: 173-183.
    CrossrefPubMedSearch in Google Scholar
  • 18 Njau F, Ness T, Wittkop U. et al. No correlation between giant cell arteritis and Chlamydia pneumoniae infection: investigation of 189 patients by standard and improved PCR methods. J Clin Microbiol 2009; 47: 1899-1901.
    CrossrefPubMedSearch in Google Scholar
  • 19 Numano F, Okawara M, Inomata H, Kobayashi Y. Takayasu’s arteritis. Lancet 2000; 356: 1023-1025.
    CrossrefPubMedSearch in Google Scholar
  • 20 Rittner HL, Hafner V, Klimiuk PA. et al. Aldose reductase functions as a detoxification system for lipid peroxidation products in vasculitis. J Clin Invest 1999; 103: 1007-1013.
    CrossrefPubMedSearch in Google Scholar
  • 21 Rittner HL, Kaiser M, Brack A. et al. Tissue-destructive macrophages in giant cell arteritis. Circ Res 1999; 84: 1050-1058.
    CrossrefPubMedSearch in Google Scholar
  • 22 Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med 2002; 347: 261-271.
    CrossrefPubMedSearch in Google Scholar
  • 23 Schirmer M, Duftner C, Seiler R. et al. Abdominal aortic aneurysms – an underestimated type of immune-mediated large vessel arteritis?. Curr Opin Rheumatol 2006; 18: 48-53.
    CrossrefPubMedSearch in Google Scholar
  • 24 Seko Y, Minota S, Kawasaki A. et al. Perforin- secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu’s arteritis. J Clin Invest 1994; 93: 750-758.
    CrossrefPubMedSearch in Google Scholar
  • 25 Seko Y, Sato O, Takagi A. et al. Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in aortic tissue of patients with Takayasu’s arteritis. Circulation 1996; 93: 1788-1790.
    CrossrefPubMedSearch in Google Scholar
  • 26 Seko Y, Sugishita K, Sato O. et al. Expression of costimulatory molecules (4–1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu’s areteritis. J Vas Res 2004; 41: 84-90.
    Search in Google Scholar
  • 27 Streetz KL, Wustefeld T, Klein C. et al. Mediators of inflammation and acute phase response in the liver. Cell Mol Biol 2001; 47: 661-673.
    PubMedSearch in Google Scholar
  • 28 Wagner AD, Bjornsson J, Bartley GB. et al. Interferon- gamma-producing T cells in giant cell vasculitis represent a minority of tissueinfiltrating cells and are located distant from the site of pathology. Am J Pathol 1996; 148: 1925-1933.
    PubMedSearch in Google Scholar
  • 29 Wagner AD, Dejaco C. Notfall Rheumatologie: Riesenzellarteriitis mit Sehstörungen, vertebrobasilärer oder anderweitiger akuter arterieller Insuffizienz. Aktuel Rheumatol 2010; 35: 43-48.
    Thieme ConnectSearch in Google Scholar
  • 30 Wagner AD, Gerard H, Fresemann T. et al. Detection of Chlamydia pneumoniae in giant cell vasculitis and correlation with the topographical arrangement of tissue-infiltrating dendritic cells. Arthritis Rheum 2000; 43: 1543-1551.
    CrossrefPubMedSearch in Google Scholar
  • 31 Wagner AD, Goronzy JJ, Weyand CM. Functional profile of tissue-infiltrating and circulating CD68+ cells in giant cell arteritis. Evidence for two components of the disease. J Clin Invest 1994; 94: 1134-1140.
    CrossrefPubMedSearch in Google Scholar
  • 32 Weyand CM, Goronzy JJ. Arterial wall injury in giant cell arteritis. Arthritis Rheum 1999; 42: 844-853.
    CrossrefPubMedSearch in Google Scholar
  • 33 Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatica. Ann Intern Med 2003; 139: 505-515.
    CrossrefPubMedSearch in Google Scholar
  • 34 Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003; 349: 160-169.
    CrossrefPubMedSearch in Google Scholar
  • 35 Weyand CM, Goronzy JJ. Pathogenesis of mediumand large-vessel vasculitis. Z Rheumatol 2009; 68: 100-107.
    CrossrefPubMedSearch in Google Scholar
  • 36 Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann Intern Med 1994; 121: 484-491.
    CrossrefPubMedSearch in Google Scholar
  • 37 Weyand CM, Wagner AD, Bjornsson J, Goronzy JJ. Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis. J Clin Invest 1996; 98: 1642-1649.
    CrossrefPubMedSearch in Google Scholar
  • 38 Wipfler-Freißmuth E, Loock J, Moosig F. et al. Aktuelle Therapieansätze bei Riesenzellarteritiden. Z Rheumatol 2009; 68: 132-136.
    CrossrefPubMedSearch in Google Scholar