title: [Clinical significance of anti-neutrophil cytoplasmic antibody and pathogenetic role of adhesion molecules for Wegener's granulomatosis].
abstract: Anti-neutrophil cytoplasmic antibodies (ANCA) have been reported as a disease-specific marker for Wegener's granulomatosis (WG). In present study I have reported clinical significance of ANCA and pathogenetic role of adhesion molecules for WG. ANCA have been detected mainly by indirect immunofluorescence assay (IIF). I have developed an enzyme-linked immunosorbent assay (ELISA) for determining and quantifying ANCA. Based on the findings that the C-ANCA-related antigen is localized in alpha-fraction of neutrophils, I purified the alpha-fraction from supernatants of homogenized neutrophils by the sucrose gradient centrifugation and used it as an antigen. Peroxidase conjugated rabbit anti-human IgG was used as a secondary antibody. ELISA units in sera from 25 healthy donors were all below 10 units, so the limit for positive ELISA readings was set up 10 units. All of 20 patients with WG in active stage were positive and 7 of them showed high units more than 100 units. Among 19 patients with WG in inactive stage, 8 patients were positive, but only one showed high units. Among 32 patients with collagen diseases other than WG, 14 patients were positive, but 11 of the 14 showed P-ANCA positive on IIF. Since myeloperoxidase (MPO) is a major component of the alpha-fraction, the performance of the ELISA has also been evaluated for sera containing anti-MPO antibody. But the ELISA units correlated individually with the IIF titers and monitored disease activities. This ELISA provides precise ANCA quantitation and will be useful for the diagnosis of WG and for monitoring its activity. According to current concepts of pathogenesis in WG, the adhesion of neutrophils to the endothelial cells appears to be important for vasculitis. In this study, I observed that level of soluble inter-cellular adhesion molecule-1 (sICAM-1) had tendency to reflect disease activities in WG.
authors.affiliation: Department of Otolaryngology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takizawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D011817:Rabbits
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D018799:Intercellular Adhesion Molecule-1