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Related Experiment Video

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Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
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Complement in ANCA-associated glomerulonephritis.

Marc Hilhorst1, Pieter van Paassen1,2, Henk van Rie1,3

  • 1Clinical & Experimental Immunology, Cardiovascular Research Centre Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|August 16, 2015
PubMed
Summary

Complement activation, particularly via the alternative pathway, is implicated in ANCA-associated glomerulonephritis, even without visible immune deposits. C3d and properdin staining correlate with more severe kidney damage in these patients.

Keywords:
ANCAcomplementglomerulonephritisrenal biopsy

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Area of Science:

  • Nephrology
  • Immunology
  • Pathology

Background:

  • Anti-neutrophil cytoplasmic antibodies (ANCA) are linked to pauci-immune necrotizing crescentic glomerulonephritis.
  • The role of complement in ANCA-associated vasculitis (AAV) was previously underestimated.
  • Recent studies suggest complement inhibition reduces glomerular damage in AAV mouse models.

Purpose of the Study:

  • To investigate whether immune complex formation or deposition triggers complement activation in ANCA-associated glomerulonephritis.
  • To explore the role of the complement system in the pathogenesis of AAV.

Main Methods:

  • Analysis of renal histology, immunoglobulin, and complement immunofluorescence in ANCA-positive patients.
  • Staining for C3d, properdin, C4d, and mannose-binding lectin (MBL).
  • Electron microscopy and assessment of circulating immune complexes and C3 allotypes.

Main Results:

  • C3c and C3d deposition was observed in a significant portion of AAV renal biopsies, varying between PR3-AAV and MPO-AAV.
  • Properdin staining was more prevalent in biopsies with crescentic features.
  • Biopsies positive for C3d and/or properdin showed increased cellular crescents and reduced normal glomeruli.

Conclusions:

  • Immune complex deposits were largely absent in AAV renal biopsies, suggesting rapid degradation.
  • Complement activation, indicated by C3d, C4d, and C5b-9 staining, is common in AAV.
  • Findings support the hypothesis of predominant alternative pathway activation in AAV pathogenesis.