Antineutrophil cytoplasmic antibody-associated glomerulonephritis with immunoglobulin deposition

Clin Exp Nephrol. 2017 Aug;21(4):643-650. doi: 10.1007/s10157-016-1341-1. Epub 2016 Nov 9.

Abstract

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is commonly classified as pauci-immune glomerulonephritis; however, some cases have granular immunoglobulin deposition along the glomerular capillary. The pathogenesis of immune deposits is poorly studied.

Methods: Of 66 patients diagnosed with ANCA-associated glomerulonephritis on renal biopsy, cases with immunoglobulin deposition along the glomerular capillary were identified and their clinicopathological characteristics were analyzed. We also performed myeloperoxidase (MPO) and double immunofluorescence (IF) stainings to determine the presence of immune complex antigens.

Results: Granular IgG deposition, IgG plus IgM deposition, and IgM deposition were observed in 15 (22.1%), 8 (11.2%), and 17 (25.0%) cases, respectively. In cases with granular IgG deposition, MPO-IgG double IF staining revealed co-localization of MPO and IgG. In cases with granular IgM deposition, MPO-IgM double IF staining did not co-localize. By electron microscopy, subepithelial deposition as well as intramembranous, subendothelial, and mesangial deposition was detected in the patients with IgG deposition. In addition, renal survival curves were not significantly different between the immunoglobulin deposition and non-deposition groups.

Conclusions: Granular IgG and/or IgM deposition was observed in 60.6% of patients with ANCA-associated glomerulonephritis. In cases with IgG deposition, electron-dense deposits (EDDs) were observed at various sites in the glomerulus, and MPO and IgG immunocomplex deposition was frequently observed along the glomerular capillary. With IgM deposition, EDDs were not obvious in the glomerular basement membrane, and MPO and IgM immunocomplex was not detected. These data suggest differential mechanism between IgG deposition and IgM deposition.

Keywords: ANCA; Histopathology; Immunocomplex; Immunoglobulin; MPO.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / analysis*
  • Biomarkers / analysis
  • Biopsy
  • Capillaries / immunology
  • Capillaries / pathology
  • Disease Progression
  • Female
  • Fluorescent Antibody Technique
  • Glomerular Basement Membrane / immunology
  • Glomerular Basement Membrane / pathology
  • Glomerulonephritis / classification
  • Glomerulonephritis / diagnosis
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / therapy
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulin G / analysis*
  • Immunoglobulin M / analysis*
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / immunology*
  • Kidney Glomerulus / ultrastructure
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Peroxidase / analysis
  • Renal Replacement Therapy
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Biomarkers
  • Glucocorticoids
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents
  • Peroxidase