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Der Nephrologe

, Volume 7, Issue 3, pp 192–199 | Cite as

ANCA-assoziierte Vaskulitiden

Neuere Aspekte der Entstehung
  • A. Schreiber
  • M. Choi
  • R. KettritzEmail author
Leitthema
  • 312 Downloads

Zusammenfassung

Antineutrophile zytoplasmatische Antikörper (ANCA) finden sich bei Patienten mit Vaskulitiden der kleinen Gefäße und isolierter nekrotisierender extrakapillär-proliferativer Glomerulonephritis. Die Entstehung der ANCA ist Folge einer komplexen Interaktion zwischen Antigenpräsentation, T- und B-Zellen. Die Hauptzielantigene sind Proteinase 3 (PR3) und Myeloperoxidase (MPO). Hinsichtlich der ANCA-Antigene wurden neue Befunde für das lysosomal assoziierte Membranprotein-2 (LAMP-2), den Membran-PR3-Komplex und die epigenetischen Regulationen der PR3- und MPO-Transkription erhoben. Die Rolle von T-Zellen ist wenig verstanden, wobei sich die Rolle verschiedener CD4+T-Zell-Typen herauskristallisiert. Ein komplementäres PR3-Protein wurde identifiziert, das neben der Bildung antiidiotypischer PR3-ANCA auch Antikörper gegen Bestandteile der Gerinnungskaskade hervorruft. Mit der Bildung DNA-haltiger „neutrophil extracellular traps“ (NETs), der Aktivierung einer spezifischen Phosphatidylinositol-3-Kinase-Isoform und der neutrophilen serinproteasenabhängigen Interleukin-1β-Generation wurden weitere wichtige Effektorfunktionen von ANCA-stimulierten Neutrophilen und Monozyten identifiziert. Tiermodelle erlauben es, auf diese neuen Moleküle ausgerichtete Behandlungsstrategien zu testen.

Schlüsselwörter

Vaskulitis Antineutrophile zytoplasmatische Antikörper Pathogenese Leukozyten Tiermodelle 

Antineutrophil cytoplasmic antibody-associated vasculitis

Novel aspects in the pathogenesis

Abstract

Antineutrophil cytoplasmic antibodies (ANCA) occur in patients with small vessel vasculitis and necrotizing crescentic glomerulonephritis. The main target antigens are proteinase 3 (PR3) and myeloperoxidase (MPO). Novel findings implicate lysosomal-associated membrane protein 2 (LAMP-2) as an additional antigen and epigenetic mechanisms as important transcriptional regulators for PR3 and MPO expression. Generation of ANCAs is a consequence of a complex interplay between antigen presentation, T-cells and B-cells. Recent data underline the significance of distinct CD4+T-cell subsets. A complementary PR3 protein has been identified which not only triggers the generation of anti-idiotypic antibodies recognizing PR3 but also constituents of the coagulation cascade. Additional important ANCA-induced neutrophil and monocyte effector functions were identified, such as the formation of DNA-containing neutrophil extracellular traps (NETs), the activation of a specific phosphatidylinositol-3 kinase isoform and the neutrophil serine protease-dependent IL-1β generation. Animal models allow testing of treatment strategies which target these new molecules.

Keywords

Vasculitis Antineutrophil cytoplasmic antibodies Pathogenesis Leukocytes Animal models 

Notes

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Nephrologie und Internistische Intensivmedizin, Virchow-Klinikum und Experimental and Clinical Research CenterCharité Universitätsmedizin BerlinBerlinDeutschland

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