Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice:pathogenetic role in experimental vasculitis

Yaron Tomer, Boris Gilburd, Miri Blank, Ofer Lider, Rami Hershkoviz, Perina Fishman, Rosa Zigelman, Piere‐Luigi ‐L Meroni, Alan Wiik, Yehuda Shoenfeld

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Objective. To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG). Methods. BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis. Results. Mice immunized with human ANCA developed anti‐human ANCA and anti–anti‐human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. Conclusion. The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.

Original languageEnglish (US)
Pages (from-to)1375-1381
Number of pages7
JournalArthritis & Rheumatism
Volume38
Issue number10
DOIs
StatePublished - Oct 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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