Background: According to several experimental studies, antineutrophil cytoplasmic antibodies (ANCA) are involved in the pathogenesis of tissue injury in some systemic vasculitis and glomerulonephritis by stimulating oxygen radical release and secretion of lysosomal enzymes from neutrophilic granulocytes. In our work, we studied the effect of ANCA-positive sera on the ingestion and killing of C. albicans by granulocytes from healthy persons. METHODS AND RESULTS. Neutrophils isolated from the blood of healthy persons were incubated with live C. albicans in ratio 1:1 in the presence of pooled sera (controls) and 10 sera from 8 patients with ANCA-associated diseases: 6x Wegener's granulomatosis, 1x idiopathic rapidly progressive glomerulonephritis, 1x rapidly progressive glomerulonephritis concomitantly ANCA and anti-GBM (glomerula bas. membrane) positive. ANCA-positive sera did not influence the ingestion of C. albicans, but strongly inhibited killing of C. albicans (55-80% in comparison to controls). Sera from 2 patients in the time of ANCA-negativization showed lower inhibition (5 and 35%, respectively).
Conclusions: We demonstrated inhibitory effect of ANCA-positive sera on candidacidal activity of neutrophils from healthy persons. This fact could be one of the pathogenetic mechanisms of granuloma formation in Wegener's granulomatosis. Results of our experiment could be an additional rationale for the administration of trimethoprim/sulfamethoxazole as prevention of relapses of systemic vasculitis.