Renal expression of ICAM-1 and VCAM-1 in ANCA-associated glomerulonephritis--are there differences among serologic subgroups?

Clin Nephrol. 2006 Feb;65(2):79-86. doi: 10.5414/cnp65079.

Abstract

Background: Antineutrophil cytoplasmic autoantibodies (ANCA) play a role in the expression of adhesion molecules. Differences in ANCA test results in ANCA-associated vasculitis may provide differences in their renal expression.

Patients and methods: We assessed the renal expression of ICAM-1 and VCAM-1 with monoclonal antibodies in 19 patients with ANCA-vasculitis: 7 microscopic polyangiitis, 5 Wegener's granulomatosis, 4 renal-limited vasculitis and 3 Churg-Strauss disease. Immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA-testing. 10 normal renal tissues were used as controls.

Results: The ANCA staining pattern was perinuclear in 14 patients, with MPO-ANCA 31 - 220 EU/ml, and cytoplasmic in 5, with PR3-ANCA 37 - 144 EU/ml. Abnormal tubular expression of ICAM-1 and VCAM-1 was seen in more than 80% of biopsies and abnormal expression of VCAM-1 in glomerular tuft was seen in 60%. Glomerular tuft stains of ++ or +++ for VCAM-1 were observed in 10% of renal biopsies from MPO-ANCA-GN patients, but in 60% of biopsies from PR3-ANCA-GN patients (Fi = 8.538, p = 0.03).

In conclusion: De novo expression of VCAM-1 on glomerular tuft suggests that the endothelial cells play a role in ANCA-GN. De novo glomerular expression of VCAM-1 is associated more with ANCA directed against PR3 than with ANCA directed against MPO. Upregulated glomerular expression of VCAM-1 may reflect a higher histological activity in patients with PR3-ANCA, and supports the existence of specific immune activation mechanisms in the different serologic subgroups in ANCA-GN. The de novo tubular expression of ICAM-1 and VCAM-1 suggests that the epithelial cells may participate in adhesive interactions in ANCA-GN.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / metabolism*
  • Biopsy
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glomerulonephritis / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Male
  • Middle Aged
  • Myeloblastin
  • Peroxidase / blood
  • Serine Endopeptidases / blood
  • Serologic Tests
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Peroxidase
  • Serine Endopeptidases
  • Myeloblastin