'Classic' anti-neutrophil cytoplasmic autoantibodies (cANCA), 'Wegener's autoantigen' and their immunopathogenic role in Wegener's granulomatosis

Wolfgang L. Gross*, ELENA Csernok, Brigitte K. Flesch

*Korrespondierende/r Autor/-in für diese Arbeit
46 Zitate (Scopus)

Abstract

Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG). WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7. Like other lysosomal proteins, WA/PR3 displays enzymzatic activity, differentiation factor activity for myeloid precursor cells, and antimicrobial functions. Neutrophilic polymorphonuclear leukocytes (PMN) and a subpopulation of monocytes contain high levels of WA/PR3 in their myeloperoxidase-positive granules. The autoantibodies from WG sera produce a finely granular, centrally accentuated fluorescence pattern on PMN and monocytes and have been designated 'classic' pattern antineutrophil cytoplasmic autoantibodies (cANCA). However, PMN/monocyte activation (in vitro/ex vivo) is associated with the translocation of WA/PR3 on the cytoplasm membrane. WA/PR3 is accessible to the WG-associated autoantibody: cANCA stimulate cytokine-preactivated PMN to produce oxygen radicals and to degranulate. Furthermore, cANCA interfere with the biological functions of WA/PR3 (e.g. inhibition of elastinolytic activity). Hence, cANCA represents not only the best seromarker for WG so far available, but several lines of evidence indicate that the autoantibodies against WA/PR3 play a major role in the pathogenesis of this enigmatic disease.

OriginalspracheEnglisch
ZeitschriftJournal of Autoimmunity
Jahrgang6
Ausgabenummer2
Seiten (von - bis)171-184
Seitenumfang14
ISSN0896-8411
DOIs
PublikationsstatusVeröffentlicht - 04.1993

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

Fingerprint

Untersuchen Sie die Forschungsthemen von „'Classic' anti-neutrophil cytoplasmic autoantibodies (cANCA), 'Wegener's autoantigen' and their immunopathogenic role in Wegener's granulomatosis“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren