Renal histopathology

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Introduction and Aims: Pauci-immune necrotizing glomerulonephritis (PINGN) with antineutrophil cytoplasmic autoantibody (ANCA) are observed in systemic vasculitis (Microscopic polyangiitis [MPA] with or without granuloma) but can be isolated and considered as vasculitis limited to the kidney. By immunofluorescence, very few immmunoglobulin deposits can be observed associated with some C3 deposits. Recent studies in murine models indicate that complement alternative pathway is involved in the development of necrotizing glomerulonephritis. We seeked to analyse the deposition of complement activation products in kidney biopsies of PINGN, using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Methods: Renal biopsies from 11 patients with PR3-ANCA and 8 patients with MPO-ANCA (5 MPA without granuloma, 3 isolated PINGN) were studied with anti-C3d (IHC), anti-C4d (IHC) and anti-C5b-9 (IF) antibodies and compared to C3c deposits observed with standard IF in glomeruli. Control biopsies were 2 cases of PINGN without C3c deposits, 1 case of acute post infectious glomerulonephritis with C3c granular deposits, and one normal kidney biopsy. Results: 10 of 11 renal biopsies from patients with PR3-ANCA had a moderate segmental or diffuse granular C3d staining in 38,5% of glomeruli, with identical localisation compared to C3c deposits. A C4d staining was noted in the same localization as C3d but with milder intensity and in only 4 cases. C5b-9 studied in the 10 cases with IF available showed a moderate to intense granular deposit in the flocculus (along glomerular basement membrane in 1 case). The 8 renal biopsies from patients with MPO-ANCA had a strong granular C3d staining in 57% of glomeruli. As for PR3-ANCA biopsies, C4d was positive only in 5 of 8 renal biopsies. C5b-9 staining was positive in the 4 cases tested with IF available. The C5b-9 staining was similar in the two groups, but in the MPO group, some segmental accumulation was observed in segmental lesions corresponding to crescents and necrosis. In control biopsies, C5b-9 was absent in glomerulus floculus of normal kidney but had identical distribution in acute post infectious glomerulonephritis. Conclusions: Complement pathways activation products, including those of the classical alternative pathway, are detected in the glomeruli of patients with PINGN. We have observed a more intense staining of C3d in patients with MPO-ANCA compared to patients with PR3-ANCA, which may reflect the more chronic/subacute course of MPO-PINGN compared to PR3-PIGN.

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