Pathogenese des systemischen Lupus erythematodes

Zusammenfassung

Der systemische Lupus erythematodes (SLE) ist eine Autoimmunerkrankung, die durch eine Vielzahl klinischer Manifestationen und die Beteiligung verschiedener Organe gekennzeichnet ist. Charakteristisch ist das Auftreten von Antikörpern gegen nukleäre Antigene. Die Ablagerung von Immunkomplexen und die Aktivierung des Komplementsystems führen schließlich zur systemischen Inflammation und zur Schädigung verschiedenster Organsysteme. Letztendlich sind die dieser systemisch entzündlichen Autoimmunerkrankung zugrunde liegenden Mechanismen bis heute nur teilweise verstanden. Zentral an der Pathogenese des SLE beteiligt scheinen jedoch eine Fehlregulation des apoptotischen Zelltodes bzw. eine Störung in der nichtentzündlichen Beseitigung apoptotischer Zellen durch professionelle Phagozyten. Nukleäre Autoantigene akkumulieren im Zytoplasma apoptotischer Zellen oder werden sogar auf deren Oberfläche exprimiert. Somit kommen apoptotische Zellen als Quelle der Autoantigene in Frage, gegen die sich die Autoimmunantwort bei SLE-Patienten richtet. Schließlich wurde erst kürzlich auch subzellulären Partikeln, die von apoptotischen Zellen freigesetzt werden und ebenfalls verschiedenste Autoantigene beinhalten, eine Rolle in der Pathogenese des SLE zugesprochen. Der vorliegende Beitrag soll neue Erkenntnisse zur SLE-Pathogenese zusammengefasst darstellen.

Summary

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of clinical manifestations involving various organ systems. A characteristic of SLE is the occurrence of autoantibodies against nuclear antigens. Deposition of immune complexes and activation of the complement system finally causes damage to different organ systems. However, the molecular mechanisms underlying this systemic inflammatory autoimmune disease are only partially understood to date. A dysregulation of apoptosis and the non-inflammatory phagocytic clearance of apoptotic cells is discussed as a central pathogenic mechanism in SLE. Nuclear autoantigens accumulate in the cytoplasm of apoptotic cells or are even exposed on their surface. Thus, apoptotic cells in fact represent a source of the antigens, which are targeted in an autoimmune reaction in SLE patients. Finally subcellular particles which contain a variety of autoantigens and released from apoptotic cells have been discussed to be involved in SLE pathogenesis. In this article recent findings on the pathogenesis of SLE are summarized.

Schlüsselwörter

Systemischer Lupus erythematodes - Apoptose - Immunkomplexe - Mikropartikel - Interferon Typ I

Keywords

Systemic lupus erythematosus - apoptosis - immune complexes - microparticles - type I interferon

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