Ätiologie und Pathogenese der Polymyalgia rheumatica und Riesenzellarteritis

C. Dejaco; A. D. Wagner

doi:10.1055/s-0034-1383661

Aktuelle Rheumatologie, Inhaltsverzeichnis

Aktuelle Rheumatologie 2014; 39(04): 256-260
DOI: 10.1055/s-0034-1383661

Übersichtsarbeit

Ätiologie und Pathogenese der Polymyalgia rheumatica und Riesenzellarteritis

Aetiology and Pathogenesis of Polymyalgia Rheumatica and Giant-cell Arteritis

Autoren

C. Dejaco

¹Klinische Abteilung für Rheumatologie, Medizinische Universität Graz, Graz, Österreich
A. D. Wagner

²Abteilung für Nephrologie, Medizinische Hochschule Hannover, Hannover

Abstract

Zusammenfassung

Der Polymyalgia rheumatica (PMR) und die Riesenzellarteritis (RZA) sind eng assoziierte Krankheitsbilder unklarer Ätiologie. Neben genetischen Faktoren wie weibliches Geschlecht, Polymorphismen im HLA Klasse II Gen sowie Varianten in Genen für Adhäsionsmoleküle und Chemokine spielen vermutlich auch Infektionen eine zentrale Rolle. Serologische Untersuchungen und Gewebeanalysen auf diverse virale und bakterielle Erreger (insbesondere Parvovirus B19 und Chlamydia pneumoniae) lieferten bisher aber widersprüchliche Ergebnisse. Alterungsprozesse des Immun- und Gefäßsystems wie die Ansammlung pro-inflammatorischer Zytokine und die Häufung oxidativer Endprodukte, sowie Störungen der endokrinen Achsen (z. B. inadäquat niedrige endogene Kortisolproduktion, Verlust von Androgenen) könnten zusätzlich zur Entstehung der PMR und RZA beitragen. Entscheidend für die Entzündungsreaktion ist die abnorme Reifung dendritischer Zellen in der Gefäßwand. Aktivierte dendritische Zellen rekrutieren bei der RZA (nicht aber bei der PMR) IFN-γ produzierenden CD4+ T-Zellen und Makrophagen in die Gefäßwand, welche durch Produktion von Matrix Metalloproetinasen eine Zerstörung der glatten Muskelzellen und eine Fragmentierung der Membrana elastica interna hervorrufen. Wachstumsfaktoren wie Platelet-derived growth factor (PDGF) und Vascular endothelial growth factor (VEGF) welche im nachfolgenden Reparationsprozess sezerniert werden, rufen einen Intimahyperplasie hervor, die schlussendlich zum Verschluss des betroffenen Gefäßes führt.

Abstract

Polymyalgia rheumatica (PMR) and giant-cell arteritis (GCA) are closely related conditions with unclear aetiology. Genetic factors including female sex and polymorphisms in the HLA II gene, adhesion molecules and chemokines, as well as infections may play important roles in the pathogenesis of the disease. Serological and tissue analyses for viral and bacterial agents (including Parvovirus B19 and Chlamydia pneumoniae), however, revealed conflicting results. Age-related changes of the immune and vascular system with the accumulation of pro-inflammatory cytokines and oxidative end-products as well as abnormalities in the endocrine axes (e. g., inadequate low endogenous cortisol production, loss of androgens) may all together contribute to the disease process. In GCA but not in PMR, abnormal maturation of dendritic cells leads to the recruitment of IFN-γ producing CD4+ T-cells and macrophages into the vessel wall. Macrophages produce matrix metalloproteinases causing a destruction of small muscle cells and the internal elastic membrane. They also release growth factors including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) leading to intima hyperplasia and vascular occlusion.

Schlüsselwörter

Polymyalgia rheumatica - Riesenzellarteritis - T-Zellen - Ätiologie

Key words

polymyalgia rheumatica - giant cell arteritis - T-cells - etiology

Volltext

Referenzen

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