Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings

Abstract

Background: Leukocyte adhesion molecules are important for migration of the inflammatory cells into sites of inflammation. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily that are expressed in normal kidney. Their expression is up-regulated in the renal tissue of patients with lupus nephritis (LN).

Objectives: We evaluated whether changes in urinary levels of ICAM-1 and VCAM-1 reflect renal tissue damage in LN. We related the levels of these molecules to other laboratory findings, especially complement C3/C4 levels. We also tested the hypothesis that changes in urinary levels of ICAM-1 and VCAM-1 reflect the severity of renal tissue damage in LN.

Patients and methods: This study included 30 systemic lupus erythematosus (SLE) patients with LN (16 with mild histological changes, i.e., with World Health Organization (WHO) class I and II LN, and 14 with advanced histological changes, i.e., class III, IV, and V LN) and 20 with SLE without nephritis. In addition, 20 healthy individuals of comparable age were included as a control group. The levels of urinary ICAM-1 and VCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) and related to the clinical, laboratory [rheumatoid factor(RF), antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), complements C3 and C4] and histological findings.

Results: Levels of urinary ICAM-1 and VCAM-l in LN patients with advanced histological changes (renal damage) were statistically significantly higher than those in other groups (LN patients with mild histological changes or SLE patients without nephritis and control group; p < 0.01). In contrast, serum levels of C3 and C4 in LN patients with advanced histological changes were significantly lower than those in other groups (p < 0.01). There was a significant negative correlation between the levels of urinary adhesion molecules and serum complement levels (p < 0.01).

Conclusions: The significantly high urinary levels of the adhesion molecules in the LN group with advanced histological changes may reflect their renal tissue expression and therefore the severity of the nephritis. Renal tissue damage in these cases may be the result of transmigration of activated inflammatory cells, inducing serious tissue damage. The hypocomplementemia combined with increased urinary levels of adhesion molecules seems to be a useful biomarker of disease severity in LN.