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Translationale Forschung in der pädiatrischen Rheumatologie

Aktuelle Forschungsansätze zum angeborenen Immunsystem

Translational research in pediatric rheumatology

Current research approaches to the innate immune system

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Zusammenfassung

Durch translationale Forschung werden Grundlagenforschung und Klinik eng miteinander verknüpft, indem die in einem Bereich gewonnenen Erkenntnisse zu Fortschritten im jeweils anderen Bereich führen können. Insbesondere in der Kinderrheumatologie hat diese Vorgehensweise in den vergangenen Jahren das Verständnis und die Therapie zahlreicher Erkrankungen wesentlich verbessert. Sogenannte DAMPs („damage associated molecular pattern“) wie die S100-Proteine, ihre Struktur, Sekretion und Funktion in inflammatorischem Geschehen stehen dabei im Zentrum unserer Forschungen. Als potenzielle Biomarker für eine spezifischere Diagnostik der (Auto-)Inflammation sind sie von besonderem klinischem Interesse. Überaktivierte Zellen des angeborenen Immunsystems spielen eine entscheidende Rolle bei der Entstehung rheumatischer Erkrankungen. So wurden Mechanismen wie die NETosis (Bildung von „neutrophil extracellular traps“) mit der Pathogenese von entzündlichen Erkrankungen wie systemischem Lupus erythematodes oder rheumatoider Arthritis in Zusammenhang gebracht. Außerdem zeigt sich zunehmend, dass die dabei dominierende sterile und überschießende Entzündungsreaktion über verschiedenste Wege zu einer Aktivierung der adaptiven Immunantwort und somit zur Entwicklung von Autoimmunität beitragen kann. Die Erforschung dieser potenziell DAMP-abhängigen Signalwege zwischen angeborenem und erworbenem Immunsystem kann ein besseres Verständnis kinderrheumatologischer Erkrankungen ermöglichen. Auf diese Weise können mögliche neue Angriffspunkte identifiziert werden, um aktuelle Therapiemöglichkeiten immer weiter zu optimieren.

Abstract

Translational research aims at closely linking basic research and clinical observations so that important mechanistic insights identified in one field should trigger progress in the other. Particularly in the field of pediatric rheumatology this approach has significantly improved the understanding and therapy of several diseases in recent years. One focus of our research in this respect is on the structure, release mechanisms and function of damage associated molecular patterns (DAMP), particularly S100 proteins. Due to their huge potential as inflammation biomarkers for more specific diagnostics these proteins are of particular clinical interest. Overactivated cells of the innate immune system play a crucial role in the development of rheumatic diseases. Innate mechanisms, such as the generation of neutrophil extracellular traps (NETosis) were linked to the pathogenesis of inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, it became increasingly more evident that various excessive sterile inflammatory mechanisms and reactions significantly contribute to an activation of adaptive immune responses and thus to the development of autoimmunity. Studying such potentially DAMP-dependent pathways at the interface between innate and adaptive immunity can provide a better understanding of autoinflammatory conditions in pediatric rheumatology and to identify novel targets for optimization of therapy.

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Authors and Affiliations

  1. Klinik für Pädiatrische Rheumatologie und Immunologie, Universitätsklinikum Münster, Domagkstraße 3, 48149, Münster, Deutschland

    K. Lippitz, J. Waldkirch, C. Kessel, G. Varga &  D. Foell

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  1. K. Lippitz
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  2. J. Waldkirch
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  3. C. Kessel
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  4. G. Varga
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  5. D. Foell
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Correspondence to D. Foell.

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Interessenkonflikt

K. Lippitz, J. Waldkirch, C. Kessel, G. Varga und D. Foell geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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H.-I. Huppertz, Bremen

K. Lippitz und J. Waldkirch teilen sich die Erstautorenschaft.

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Lippitz, K., Waldkirch, J., Kessel, C. et al. Translationale Forschung in der pädiatrischen Rheumatologie. Z Rheumatol 75, 276–283 (2016). https://doi.org/10.1007/s00393-015-0040-8

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