Pathogenese der Einschlusskörperchenmyositis: Stellenwert der Entzündung und Bedeutung für Therapiestrategien

Zusammenfassung

Die Einschlusskörperchenmyositis (sporadic Inclusion Body Myositis, sIBM) ist die häufigste entzündliche Myopathie bei älteren Patienten. Eine effektive Therapie ist nicht verfügbar, sodass es zu einem langsam fortschreitenden Gehverlust kommt. Die komplexe Pathogenese umfasst degenerative Mechanismen mit einer Akkumulation aberranter Moleküle, vor allem β-Amyloid. Es kommt daneben zu einer deutlichen Entzündungsreaktion im Muskel mit einer Infiltration durch zytotoxische T-Zellen. In dieser Übersicht werden neuere Arbeiten zu unterschiedlichen Pathomechanismen bei der sIBM zusammengefasst. Es konnte demonstriert werden, dass Makroautophagie an der Prozessierung von β-Amyloid beteiligt ist und in Relation zu antigenpräsentierenden Mechanismen steht. Bezüglich der zytotoxischen T-Zell-Infiltration gibt es Hinweise auf eine relevante Antigenpräsentation über sogenannte „nichtklassische”, kostimulatorische Moleküle. Des Weiteren konnte bei der sIBM eine spezifische Interaktion zwischen degenerationsassoziierten Molekülen und der Entzündung im Muskel belegt werden. Passend dazu fand sich in Muskelzellen eine Akkumulation von β-Amyloid, die durch IL-1β induziert werden konnte. Zusammengefasst belegen diese Arbeiten, dass entzündliche Pathomechanismen bei der sIBM von wesentlicher Bedeutung sind. Aktuelle Therapiestrategien umfassen eine gezielte antikörpervermittelte Blockade von T-Zellen (Alemtuzumab) und B-Zellen (Rituximab). Daneben sollte zukünftig auch die Blockierung entzündlicher Mediatoren wie IL-1β und CXCL-9 sowie von β-Amyloid-generierenden Mechanismen (BACE1, Autophagie) erwogen werden.

Abstract

Sporadic inclusion body myositis (sIBM) is the most common myopathy in older patients. An effective therapy is not available to halt the slowly progressive loss of ambulation. The complex pathology includes degenerative mechanisms with an accumulation of aberrant molecules, most of all β-amyloid. At the same time, a significant inflammation with an infiltration by cytotoxic T-cells occurs in the muscle. This review summarises recent work on different pathomechanisms of sIBM. It has been demonstrated that macroautophagy is involved in the processing of β-amyloid and related to antigen-presenting mechanisms. In view of the infiltration by cytotoxic T-cells, there is evidence of a relevant antigen presentation via so-called „non-classical” co-stimulatory molecules. Moreover, in sIBM there is a specific interrelationship between degeneration-associated molecules and inflammation in the muscle. In line with this, an accumulation of β-amyloid can be induced by IL-1β in muscle cells. Taken together, these studies demonstrate that inflammatory mechanisms are of crucial relevance to the pathology of sIBM. Current therapeutic strategies include an antibody-mediated depletion of T-cells (alemtuzumab) and B-cells (rituximab). In the future, blockade of inflammatory molecules such as IL-1β and CXCL-9 as well as of β-amyloid-associated mechanisms (BACE1, autophagy) should be taken into account.

Schlüsselwörter

Myositis - Myopathie - Autoimmunität

Key words

myositis - myopathy - autoimmunity

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