Zeitschrift für Rheumatologie

, Volume 76, Issue 4, pp 328–334 | Cite as

Klinik und Genetik bei Proteasomen-assoziierten autoinflammatorischen Syndromen (PRAAS)

Leitthema
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Zusammenfassung

Funktionsstörungen des Proteasoms können zu schweren Beeinträchtigungen des angeborenen Immunsystems führen. Diese neuen Interferonopathien mit autosomal-rezessivem Erbgang werden inzwischen als ein Erkrankungsspektrum angesehen und unter dem Oberbegriff der Proteasomen-assoziierten autoinflammatorischen Syndrome (PRAAS) zusammengefasst. In der Pathogenese werden eine Akkumulation von ubiquitinierten Proteinen und die Induktion von Typ-I-IFN-Genen angenommen. Zu den typischen klinischen Manifestationen gehören Lipodystrophie, Haut-, Gelenk- und Muskelbeteiligung mit einer bemerkenswerten Variabilität weiterer assoziierter Symptome. Dieser Beitrag gibt einen Überblick zu den aktuell bekannten molekularen Veränderungen sowie zu klinischen Gemeinsamkeiten und Unterschieden bei PRAAS. Weiterhin wird auf bisher eingesetzte immunsuppressive Therapieansätze eingegangen.

Schlüsselwörter

Immunoproteasom Lipodystrophie Immunsystem Immunsuppression Pathogenese 

Clinical aspects and genetics of proteasome-associated autoinflammatory syndromes (PRAAS)

Abstract

Functional disorders of the proteasome can have a severe impact on the innate immune system. Characterized by an autosomal recessive mode of inheritance, this novel type of interferonopathy is considered to be a spectrum of diseases of proteasome-associated autoinflammatory syndromes (PRAAS). Accumulation of ubiquitinated proteins and the induction of type I interferon (IFN) genes seem to play a role in the pathogenesis. The typical clinical manifestations are lipodystrophy, skin, joint and muscle involvement accompanied by a remarkable variability of other associated symptoms. This article provides an overview on currently known molecular alterations as well as clinical similarities and differences of PRAAS. Furthermore, the reported effects of the immunosuppressive therapy approaches used so far are summarized.

Keywords

Immunoproteasome Lipodystrophy Immune system Immunosuppression Pathogenesis 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

E. Feist, A. Brehm, T. Kallinich und E. Krüger geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Klinik für Rheumatologie und Klinische ImmunologieCharité – Universitätsmedizin BerlinBerlinDeutschland
  2. 2.Klinik für Pädiatrie m.S. Pneumologie und ImmunologieCharité – Universitätsmedizin BerlinBerlinDeutschland
  3. 3.Institut für BiochemieCharité – Universitätsmedizin BerlinBerlinDeutschland

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