Neue Erkenntnisse zur Pathogenese des SLE und ihre Auswirkungen auf die Entwicklung neuer Therapie-Konzepte

Zusammenfassung

Autoantikörper sind essentiell in der Pathogenese des SLE. Sie sind das Ergebnis einer Störung des erworbenen (adaptiven) Immunsystems mit fehlender Toleranz gegen Selbst. Eine Typ-I Interferon-Signatur, die im angeborenen (innaten) Immunsystem ihren Ursprung hat, ist ein wesentlicher Treiber dieser Störung. Autoantikörper können sowohl von kurzlebigen, proliferierenden Plasmablasten, die B-Zell-Hyperaktivität widerspiegeln, als auch von langlebigen, nicht-proliferierenden Gedächtnis-Plasmazellen sezerniert werden. Gedächtnis-Plasmazellen, die in Nischen im Knochenmark und im entzündeten Gewebe lokalisiert sind, lassen sich nicht durch konventionelle Immunsuppressiva und Therapien mit B-Zellen als Target eliminieren. Konzepte, die auf die Depletion von Gedächtnis-Plasmazellen abzielen, können im Zusammenspiel mit Targets, die eine Aktivierung von autoreaktiven B-Zellen verhindern, ein kuratives Potenzial haben.

Abstract

Autoantibodies are essential in the pathogenesis of SLE. They are the result of a disorder of the acquired (adaptive) immune system with lack of tolerance to self. A type I interferon signature, which originates in the innate immune system, is a major driver of this disorder. Autoantibodies can be secreted by both short-lived, proliferating plasmablasts reflecting B-cell hyperactivity and by long-lived, non-proliferating memory plasma cells. Memory plasma cells located in niches in bone marrow and inflamed tissue cannot be eliminated by conventional immunosuppressants and therapies with B cells as a target. Concepts aiming at the depletion of memory plasma cells may have curative potential in interaction with targets that prevent the activation of autoreactive B cells.

Schlüsselwörter

Systemischer Lupus erythematodes - Autoantikörper - Pathogenese - Plasmazelle - Therapie

Key words

Systemic lupus erythematosus - autoantibody - pathogenesis - plasma cell

Publication History

Article published online:
06 August 2020

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