Immunpathogenese und Therapie inflammatorischer Myopathien

Zusammenfassung

Die gegenwärtige Unterteilung sowie die pathogenetischen Konzepte der drei Hauptentitäten inflammatorischer Myopathien, der Polymyositis (PM), der Dermatomyositis (DM) sowie der Einschlusskörpermyositis (IBM) basieren auf einer Kombination von klinischen, histologischen und immunpathologischen Befunden. Die klassischen Pathogenesekonzepte nehmen an, dass bei der Polymyositis und bei der Einschlusskörpermyositis eine immunvermittelte Schädigung durch zytotoxische T-Zellen maßgeblich beteiligt ist. Bei der Dermatomyositis scheinen humoral vermittelte Schädigungen der Kapillaren bzw. kleinen Gefäße ursächlich. Die pathogenetische Bedeutung klonal expandierter CD8-T-Zellen in der Pathogenese der Polymyositis sowie der Einschlusskörpermyositis ist durch verschiedene Untersuchungen in den letzten Jahren gut validiert. Ebenso zeigen neuere Studien die aktive Rolle des Muskels in der direkten Interaktion mit Immunzellen und identifizieren potenzielle therapeutische Zielstrukturen für die Immunintervention. Neuere Erkenntnisse der letzten Jahre, insbesondere zur Pathogenese der Dermatomyositis, erweitern die bislang gültigen hypothetischen Pathogeneseszenarien. Während die Polymyositis und die Dermatomyositis mithilfe konventioneller immunsuppressiver Strategien (v. a. Kortikosteroide, Azathioprin) in den meisten Fällen gut kontrollierbar sind, ist die Mehrheit der Einschlusskörpermyositisfälle immuntherapeutisch kaum modulierbar. Neuere pathogenetische Erkenntnisse haben auch klare Implikationen hinsichtlich der Möglichkeiten immunselektiver Interventionen. Der gegenwärtige Stand zur Pathogenese bzw. Therapie autoimmuner entzündlicher Myopathien wird dargestellt.

Abstract

Inflammatory myopathies are currently subdivided into three main entities: polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). This categorisation is based on a combination of clinical, histological and immunopathological characteristics. The classical pathogenic concepts assume that an immune-mediated damage by cytotoxic T cells plays a major role in polymyositis and in inclusion body myositis. In dermatomyositis, humoral components directed against capillaries or small vessels are considered to be instrumental. The pathogenetic importance of clonally expanded CD8 T cells in the pathogenesis of polymyositis as well as inclusion body myositis has been well validated by various studies over the last years. Furthermore, novel studies show the active role of the muscle in the direct interaction with immune cells and help to identify the potential therapeutic target structures for immune intervention. Recent years have brought forth novel findings, particularly concerning the pathogenesis of dermatomyositis, which broaden the hypothetical scenaries for pathogenesis that have been valid so far. While polymyositis and dermatomyositis are well controllable in most cases by means of conventional immunosuppressive strategies (above all, corticosteroids, azathioprine), the disease course of most cases of inclusion body myositis can hardly be modulated. Novel pathogenetic findings also have clear implications with regard to the possibilities of immunoselective interventions. This paper surveys the current status of the pathogenesis of and/or therapy for autoimmune inflammatory myopathies.

Schlüsselwörter

inflammatorische Myopathien - Immunpathogenese - Myositis

Key words

inflammatory myopathies - immunopathogenesis - myositis

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