DISTRIBUTION OF THE GRANULOCYTE SERINE PROTEINASES PROTEINASE-3 AND ELASTASE IN HUMAN GLOMERULONEPHRITIS

The serine proteinases proteinase 3 (PR3) and elastase are target anti gens of antineutrophil cytoplasmic autoantibodies (ANCAs), which are f ound in various systemic vasculitides with rapidly progressive glomeru lonephritis (RPGN). The expression of both proteinases was studied imm unohistologically (avidin-biotin complex method) with murine monoclona l antibodies against PR3 (WGM2) and elastase (NP 57) in 122 human rena l biopsy specimens to investigate their role in mediating renal damage . Expression of PR3 predominated in ANCA-associated RPGN and was indep endent of the serologic ANCA pattern (c-/p-ANCA). The PR3 staining pat tern was patchy and not always related to distinct granulocytes due to antigen spreading by disintegrating cells. It was found in crescentic glomeruli and the interstitium of ANCA-positive RPGN. In contrast, gl omerular and interstitial elastase staining pattern was much more gran ulocyte related and was even found in noncrescentic glomeruli in c-ANC A- and p-ANCA-positive pauci-immune RPGN. Endothelial cell and glomeru lar basement membrane-bound PR3 or elastase expression were not observ ed. A faint glomerular PR3/elastase expression was seen in Goodpasture 's syndrome and within the interstitium in crescentic mesangioprolifer ative glomerulonephritis (granulocyte related). Both serine proteinase s were found in the glomeruli in ANCA-negative acute postinfectious gl omerulonephritis. In conclusion, this study provides evidence, for the first time, for the implication of the granulocyte serine proteinases PR3 and elastase in mediating pauci-immune ANCA-positive RPGN and dif ferent forms of proliferative glomerutonephritis. The expression of AN CA antigens in ANCA-negative glomerulonephritis suggests that this fin ding is a marker of neutrophil activation. The role of circulating ant ibodies (ANCA) in mediating the development of the characteristic pauc i-immune RPGN and systemic vasculitis remains to be elucidated. (C) 19 95 by the National Kidney Foundation, Inc.