C-ANCA-positive IgG fraction from patients with Wegener's granulomatosis induces lung vasculitis in rats
Authors: WEIDEBACH, W.1; VIANA, V. S. T.1; LEON, E. P.1; BUENO, C.1; LEME, A. S.2; ARANTES-COSTA, F. M.2; MARTINS, M. A.2; SALDIVA, P. H. N.3; BONFA, E.1
Source: Clinical & Experimental Immunology, Volume 129, Number 1, July 2002 , pp. 54-60(7)
Publisher: Blackwell Publishing
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Abstract:
SUMMARY 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.Keywords: antineutrophil cytoplasmic antibodies (C-ANCA) Wegener's granulomatosis vasculitis
Document Type: Research article
DOI: 10.1046/j.1365-2249.2002.01888.x
Affiliations: 1: Division of Rheumatology and Departments of 2: Medicine and 3: Pathology, School of Medicine, University of São Paulo, SP, Brazil
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