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

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

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)i139-i145
JournalNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Issue number1
StatePublished - Jan 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


  • alternative pathway
  • anti-neutrophil cytoplasmic antibody
  • complement
  • crescentic glomerulonephritis
  • mass spectrometry
  • pauci-immune


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