The aim of the present study was to analyse in rats the ability of
C-ANCA-positive
IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total
C-ANCA-positive
IgG fraction isolated from serum of three different
Wegener's granulomatosis patients obtained before
therapy. Similarly, control rats were treated with
IgG fraction from two
rheumatoid arthritis patients (n = 7),
IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs.
Vasculitis and inflammatory infiltrate were consistently absent in rats injected with
rheumatoid arthritis IgG or saline and in 14/15 of normal
IgG treated animals. In contrast, marked
vasculitis was observed in all 18 animals injected with
C-ANCA-positive
IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of
granuloma-like lesions. A dose-response relationship was observed between
protein concentration of
C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition,
IgG fraction with undetectable
C-ANCA, obtained from one patient in remission
after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired
IgG that was positive for
C-ANCA taken before
therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of
C-ANCA in Wegener's disease.