120. DIFFERENCES IN RENAL HISTOPATHOLOGY BETWEEN PR3-ANCA-ASSOCIATED VASCULITIS AND MPO-ANCA-ASSOCIATED VASCULITIS Free

Background: Clinical and experimental data suggest a pathogenic role for antineutrophil cytoplasmic antibodies (ANCA) in ANCA-associated glomerulonephritis (AAGN), with possible differences between anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3)-ANCA. The aim of this study was to investigate differences in histopathological profile between MPO-AAGN and PR3-AAGN. Additionally, the effect of ANCA serotype on long-term renal outcome was examined.

Methods: 135 patients from 10 centers worldwide (Europe, North-America and Asia) with AAGN who underwent a diagnostic renal biopsy between 1991 and 2011 were included. Biopsies were scored on a secured website by 2 international nephropathologists from a group of 6. Data on demographics, renal outcome and diagnostic delay were collected retrospectively.

Results: 50 patients were positive for PR3-ANCA and 73 for MPO-ANCA; 12 patients were either double-positive or negative. At diagnosis, patients with MPO-AAGN were significantly older (64.5±12.0 years) than those with PR3-AAGN (57.4±12.8 years). Mean diagnostic delay did not differ between groups. MPO-ANCA-positive patients showed less focal class and more mixed class than PR3-ANCA-positive patients (P = 0.04). MPO-AAGN biopsies showed significantly more interstitial fibrosis and tubular atrophy (IFTA) than PR3-AAGN biopsies (P = 0.04). No difference was found regarding the presence of fibrinoid necrosis. On immunofluorescence, MPO-AAGN showed less C3-positive staining than PR3-AAGN (P = 0.02). We found no association between ANCA serotype and death, renal relapse or development of end-stage renal disease.

Conclusion: In this large, international, multicenter cohort, we found a different histopathological profile in MPO-AAGN compared to PR3- AAGN, characterized by a lower percentage of focal and higher percentage of mixed histopathological class, more IFTA and less C3 in MPO-AAGN. These findings could not be explained by differences in diagnostic delay between groups and therefore support a difference in pathogenesis between MPO- and PR3-AAGN.

Disclosures: None