ABSTRACT
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.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/toxicity , Granulomatosis with Polyangiitis/immunology , Immunoglobulin G/toxicity , Isoantibodies/toxicity , Lung Diseases/etiology , Vasculitis/etiology , Adult , Animals , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/immunology , Disease Models, Animal , Dose-Response Relationship, Immunologic , Female , Granuloma/etiology , Granuloma/pathology , Granulomatosis with Polyangiitis/blood , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Isoantibodies/immunology , Lung/blood supply , Lung Diseases/immunology , Lung Diseases/pathology , Rats , Rats, Wistar , Specific Pathogen-Free Organisms , Vasculitis/immunology , Vasculitis/pathologyABSTRACT
Os anticorpos anticitoplasma de neutrófilos (ANCA) são auto-anticorpos dirigigos contra as enzimas contidas nos grânulos dos neutrófilos e lisollomos de monócitos. Estão presentes em até 98 por cento dos casos de granulomatore de Wegener ativa, uma vasculite necrosante sistêmica, auxiliando no seu diagnóstico e seguimento pós-tratamento. Podem também ocorrer, com menor freqüência, nas glomerulonefrites pauci-imunes, nas poliangites microscópicas, nas doenças inflamatórias intestinais, nas colagenoses, em algumas neoplasias e doenças infecciosas. Podem ser detectados por imunofluorescência indireta (IFI), radioimunoensaio, ELISA e Western blotting. À IFI exibem dois padrões clássicos, o ANCA-C e o ANCA-P. Porém, outros padrões, diferentes dos clássicos podem ocorrer e são chamados ANCA-A ou atípicos. A grande dificuldade reside na interpretação destes testes e sua utilização na prática clínica. Assim, o objetivo deste trabalho é tornar o ANCA melhor conhecido pelos colegas não-familiarizados com o assunto e tentar esclarecer quando sua presença tem real significado clínico, evitando possíveis danos, por vezes irreversíveis, aos nossos pacientes.