Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis.

Abstract

BACKGROUND:

Complement activation plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although it remains unclear which pathway is activated. Whether pauci-immune necrotizing crescentic glomerulonephritis (pauci-immune GN) with negative ANCA serology is part of the spectrum of AAV or a different disease entity is essentially unknown.

METHODS:

We used proteomic analysis to delineate the complement profile in a series of 13 kidney biopsies of patients with pauci-immune GN, with either proteinase 3 (PR3) (five patients) or myeloperoxidase (MPO) antibodies (four patients) or with consistently negative ANCA serology (four patients). Immunofluorescence staining of glomeruli was essentially negative in the PR3-ANCA and MPO-ANCA groups, while a mild staining for C3 was seen in the ANCA-negative cases. No electron-dense deposits were found in the PR3-ANCA and MPO-ANCA groups, but mesangial and few subepithelial deposits were clearly present in the ANCA-negative specimens.

RESULTS:

Mass spectrometry revealed low spectra numbers for C3 and immunoglobulins in both PR3-positive and MPO-positive patients with minimal or no C4 and C9. In contrast, larger spectra numbers for C3, moderate spectra numbers for C9, complement factor H-related protein-1 and low spectra numbers for C4, C5 and immunoglobulins were found in the ANCA-negative cases.

CONCLUSION:

While complement activation is noted in AAV, the complement activation appears to be more prominent in the ANCA-negative glomerulonephritis. The larger amount of C3 and moderate amount of C9 in the ANCA-negative glomerulonephritis implies activation of the alternate and terminal pathway of complement, suggesting that this entity may be caused or promoted by a genetic or acquired defect in the alternative pathway.

• Authors: Sanjeev Sethi, Ladan Zand, An S De Vriese, Ulrich Specks, Julie A Vrana, Siddak Kanwar, Paul Kurtin, Jason D Theis, Andrea Angioi, Lynn Cornell, Fernando C Fervenza
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 32 Issue suppl_1 Pg. i139-i145 (Jan 01 2017) ISSN: 1460-2385 [Electronic] England
• PMID: 28391334 (Publication Type: Journal Article)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Biomarkers
• Proteome
• Peroxidase
• Myeloblastin

Topics

• Adolescent
• Adult
• Aged
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (immunology)
• Biomarkers (metabolism)
• Complement Activation (immunology)
• Female
• Glomerulonephritis (immunology, metabolism, pathology)
• Humans
• Male
• Middle Aged
• Myeloblastin (immunology)
• Peroxidase (immunology)
• Proteome (analysis)
• Proteomics (methods)
• Young Adult