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Glomerular ICAM-1 expression related to circulating TNF-alpha in human glomerulonephritis
H Yokoyama1, M Takaeda, T Wada
11st Department of Internal Medicine, Kanazawa University School of Medicine, Ishikawa, Japan. dialysis@med.kanazawa-u.ac.jp
Insights
This study shows that tumor necrosis factor alpha (TNF-alpha) correlates with intercellular adhesion molecule 1 (ICAM-1) in kidney inflammation. Soluble ICAM-1 (sICAM-1) may serve as a marker for interstitial damage in glomerulonephritis.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Cellular adhesion molecules and cytokines are implicated in glomerulonephritis pathogenesis.
- Intercellular adhesion molecule 1 (ICAM-1) plays a role in inflammatory processes within the kidney.
Purpose of the Study:
- To investigate the in vivo expression of ICAM-1 in human glomerulonephritis.
- To correlate ICAM-1 expression with serum levels of tumor necrosis factor alpha (TNF-alpha) and soluble ICAM-1 (sICAM-1).
Main Methods:
- Immunohistochemical analysis of ICAM-1 in 69 kidney biopsy specimens.
- Measurement of serum TNF-alpha and sICAM-1 levels in 43 patients.
- Correlation analysis between molecular markers and clinical/histological findings.
Main Results:
- Glomerular ICAM-1 expression correlated positively with serum bioactive TNF-alpha levels, endocapillary proliferation, and hematuria.
- Serum sICAM-1 levels were elevated in lupus nephritis and purpura nephritis, and decreased after treatment.
- sICAM-1 levels correlated with interstitial ICAM-1 expression and indicated systemic vasculitis.
Conclusions:
- Bioactive TNF-alpha may drive glomerular ICAM-1 expression in glomerulonephritis.
- Serum sICAM-1 levels show potential as a clinical biomarker for interstitial lesions and systemic vasculitis in nephritis.
Abstract:
To clarify the in vivo involvement of cellular adhesion molecules and cytokines in human glomerulonephritis, we have investigated the glomerular and interstitial expression of intercellular adhesion molecule 1 (ICAM-1) in 69 kidney biopsy specimens by immunohistochemical methods and its correlation with serum bioactive tumor necrosis factor alpha (TNF-alpha) and soluble ICAM-1 (sICAM-1) levels in 43 cases. In normal controls, glomerular ICAM-1 expression and serum TNF-alpha and sICAM-1 levels showed a mean score of 1.0 (n = 7) and were 12.1 +/- 1.5 and 187 +/- 5 ng/ml (mean +/- SEM, n = 25), respectively. ICAM-1 was positive in 68 kidneys except in 1 patient with membranous nephropathy at various degrees in glomeruli and in 72% of peritubular capillaries or venules in the interstitium. Serum-bioactive TNF-alpha levels increased in the patients with IgA nephropathy, purpura nephritis, and lupus nephritis (LN) (18.9 +/- 4.1, 32.6 +/- 13.3, and 20.9 +/- 3.5 pg/ml) and were positively correlated with the grade of glomerular ICAM-1 expression (n = 43, r = 0.57, p < 0.001), endocapillary proliferation with exudative lesions (r = 0.72, p < 0.001) and hematuria (r = 0.62, p < 0.001). Serum sICAM-1 levels were elevated in patients with LN and purpura nephritis and decreased from 312 +/- 40 to 226 +/- 21 ng/ml after methylprednisolone pulse therapy in LN (n = 9, p = 0.0285). sICAM-1 levels were positively correlated with the grade of interstitial ICAM-1 expression (r = 0.46, p < 0.05), and sICAM-1 levels (>210 ng/ml) showed high odds ratios in the interstitial ICAM-1-positive cases and systemic vasculitides such as purpura nephritis and LN (6.00, p = 0.0355; 6.50, p = 0.0216, respectively). These results suggest that bioactive TNF-alpha might relate to glomerular ICAM-1 expression associated with endocapillary lesions in human glomerulonephritis and that sICAM-1 levels may be used as a clinical marker to assess interstitial lesions in human nephritis and systemic vasculitides.