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  • Title: Distribution of the granulocyte serine proteinases proteinase 3 and elastase in human glomerulonephritis.
    Author: Mrowka C, Csernok E, Gross WL, Feucht HE, Bechtel U, Thoenes GH.
    Journal: Am J Kidney Dis; 1995 Feb; 25(2):253-61. PubMed ID: 7847352.
    Abstract:
    The serine proteinases proteinase 3 (PR3) and elastase are target antigens of antineutrophil cytoplasmic autoantibodies (ANCAs), which are found in various systemic vasculitides with rapidly progressive glomerulonephritis (RPGN). The expression of both proteinases was studied immunohistologically (avidin-biotin complex method) with murine monoclonal antibodies against PR3 (WGM2) and elastase (NP 57) in 122 human renal biopsy specimens to investigate their role in mediating renal damage. Expression of PR3 predominated in ANCA-associated RPGN and was independent of the serologic ANCA pattern (c-/p-ANCA). The PR3 staining pattern was patchy and not always related to distint granulocytes due to antigen spreading by disintegrating cells. It was found in crescentic glomeruli and the interstitum of ANCA-positive RPGN. In contrast, glomerular and interstitial elastase staining pattern was much more granulocyte related and was even found in noncrescentic glomeruli in c-ANCA- and p-ANCA-positive pauci-immune RPGN. Endothelial cell and glomerular basement membrane-bound PR3 or elastase expression were not observed. A faint glomerular PR3/elastase expression was seen in Goodpasture's syndrome and within the interstitium in crescentic mesangioproliferative glomerulonephritis (granulocyte related). Both serine proteinases were found in the glomeruli in ANCA-negative acute postinfectious glomerulonephritis. 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 different forms of proliferative glomerulonephritis. The expression of ANCA antigens in ANCA-negative glomerulonephritis suggests that this finding is a marker of neutrophil activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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