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Das Komplementsystem – ein „hot topic“ nicht nur bei Nierenerkrankungen

The complement system—a “hot topic” not only for kidney diseases

  • Schwerpunkt: Unser Immunsystem – der Staat im Staate
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Zusammenfassung

Die derzeitige große Bedeutung des Komplementsystems für die Nephrologie beruht ganz wesentlich auf neuartigen pathophysiologische und therapeutischen Erkenntnissen der letzten Jahre, die v. a. aus klinischen und genetischen Studien bei Kindern mit atypischem hämolytisch urämischem Syndrom (aHUS) gewonnen wurden. Das aHUS stellt hierbei die prototypische Systemerkrankung einer Überaktivierung des alternativen Komplementweges dar, die sich an verschiedenen Organen wie auch der Niere mit einer thrombotischen Mikroangiopathie (TMA) manifestiert. Die Erforschung der Pathomechanismen, die bei aHUS zu einer permanenten Überaktivierung des alternativen Komplementweges führen, mündeten im erfolgreichen klinischen Einsatz eines ersten Hemmers von C5b9, der terminalen Komplementkaskade, die lokal für den Gewebeschaden verantwortlich ist. Nachfolgend wurden auch angesichts des mittlerweile verfügbaren technologischen Fortschritts weitere systemische und renale Erkrankungen identifiziert, die auf einer Störung im Komplementsystem beruhen, und jetzt prinzipiell therapierbar sind. Bei diesen Erkrankungen kommt es aufgrund einer Mutation in Komplementfaktoren oder von Autoantikörpern gegen diese bei entsprechender Prädisposition und zusätzlichen Schädigungsreizen, z. B. im Rahmen von Infekten oder hormonellen Veränderungen, zu einer Dysregulation des Komplementsystems und nachfolgend zum Krankheitsausbruch.

Durch das zunehmende Wissen über die Regulation und damit die Beeinflussbarkeit der verschiedenen Komplementwege sowie v. a. durch die Entwicklung zahlreicher pharmakologischer Hemmsubstanzen des Komplementsystems hat der Stellenwert dieses phylogenetisch sehr alten Systems in der Medizin allgemein und speziell der Nephrologie in den letzten Jahren stark zugenommen und dazu geführt, dass das Komplementsystem derzeit zweifellos eines der „hot topics“ in der Medizin darstellt.

Abstract

Increasing interest in the role of the complement system in systemic and renal disease is based on new pathophysiological and therapeutic insights of the recent past and particularly in genetic analyses in children with atypical hemolytic uremic syndrome (aHUS). aHUS is the prototypical systemic disease associated with excessive activation of the alternative complement pathway and manifests in the kidney, but also in other organs as thrombotic microangiopathy (TMA). Pathomechanisms discovered to induce the overactivation of the alternative complement pathway in aHUS led to the first successful therapeutic application of a C5b9 inhibitor. This suppression of the terminal complement cascade succeeded in inhibiting local tissue damage. Thereafter, thanks to advanced modern technologies, further systemic and renal diseases associated with mutations or auto-antibodies targeting the complement pathway were identified. Hereby, disease onset is frequently associated with an additional trigger, e.g. infection or hormonal alterations/imbalances, against the background of a pre-existing predisposition of the patient.

Due to the growing understanding of the regulation, and thus the possibility of therapeutic modulation of the different complement pathways, and due to the increasing availability of a variety of drugs inhibiting the complement system, interest in complement-mediated systemic and renal disease has been steadily increasing, making it a “hot-topic” in medicine in recent years.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft (DFG) Sonderforschungsbereich (SFB) 1350, Teilprojekt C2.

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  1. Abt. Nephropathologie, Pathologisches Institut, Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Krankenhausstr. 8–10, 91054, Erlangen, Deutschland

    Kerstin Amann, Christoph Daniel & Maike Büttner-Herold

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  1. Kerstin Amann
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  2. Christoph Daniel
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Correspondence to Kerstin Amann.

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K. Amann, C. Daniel und M. Büttner-Herold geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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P. Möller, Ulm

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Amann, K., Daniel, C. & Büttner-Herold, M. Das Komplementsystem – ein „hot topic“ nicht nur bei Nierenerkrankungen. Pathologe 41, 238–247 (2020). https://doi.org/10.1007/s00292-020-00773-0

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