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


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).


CONCLUSIONS
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.
Arrizabalaga
P
P
Service of Nephrology, Hospital Clinic, Barcelona, Spain. parriza@clinic.ub.es
Solé
M
M
Iglesias
C
C
Escaramís
G
G
Ascaso
C
C
D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism*; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D009195:Peroxidase / Q000097:blood; D012697:Serine Endopeptidases / Q000097:blood; D012698:Serologic Tests; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019268:Antibodies, Antineutrophil Cytoplasmic; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin