Der systemische Lupus erythematodes – Pathogenese

In den letzten Jahren wurde das Verständnis der Pathogenese des systemischen Lupus erythematodes (SLE) wesentlich verbessert. Durch genomweite Assoziationsstudien wurden circa 80 Risikogene identifiziert, die wichtige Kontrollpunkte des Immunsystems beeinflussen und einen Toleranzverlust begünstigen. Durch vermehrte Apoptose und verringerte Clearance von Bestandteilen apoptotischer Zellen fallen bei SLE-Patienten vermehrt Kernproteine (wie Sm, SSA, SSB) an, die zur Autoantikörperbildung führen. Immunkomplexe, die aus DNA bzw. Ribonukleoproteinen mit RNA und Autoantikörpern bestehen, binden an Toll-like Rezeptoren auf dendritischen Zellen sowie Monozyten und induzieren die Bildung von Interferon alpha, dem treibenden Zytokin des SLE. Die Immunkomplexe aus DNA und Autoantikörpern induzieren eine Glomerulonephritis, da sie an die Basalmembran in den Nieren binden und dort zu einer Aktivierung des Komplementsystems und von Fc-Rezeptor exprimierenden Zellen führen. Das bessere Verständnis der Pathophysiologie ergibt für die Zukunft neue therapeutische Ansatzpunkte, die die Prognose des SLE weiter verbessern werden.

Recently, progress has been made in the understanding of the pathogenesis of systemic lupus erythematosus (SLE). In genome-wide association studies, more than 80 susceptibility genes have been identified which affect important control points of the immune system and contribute to a loss of tolerance. An enhanced rate of apoptosis and the reduction of the clearance of components of apoptotic cells result in the presence of nuclear proteins (such as Sm, SSA, SSB) in the circulation of SLE patients which induce the formation of autoantibodies. Immune complexes consisting of DNA or ribonucleoproteins with RNA and autoantibodies bind to Toll-like receptors on dendritic cells and monocytes and induce production of interferon alpha, the dominant cytokine in SLE. Immune complexes consisting of DNA and autoantibodies may induce glomerulonephritis, since they bind to basement membranes in the kidneys and activate both the complement cascade as well as cells expressing Fc receptors. A better knowledge of the pathophysiology will lead to the identification of further therapeutic targets and to an improvement of SLE prognosis.

Key words

systemic lupus erythematosus (SLE) - pathogenesis - etiology

• Literatur

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