Intercellular adhesion molecule-1 mediated interactions and leucocyte infiltration in IgA nephropathy.

Abstract

Mononuclear leucocytes have a role in IgA nephropathy (IgAN). Renal leucocyte recruitment is mediated by adhesive interactions between leucocytes and their ligands on renal cells. We have assessed interstitial and glomerular leucocytes by avidin-biotin-peroxidase with monoclonal antibodies (MA) against leucocytes (CD45), beta 2-integrin (CD18), monocyte-macrophages (CD14), T (CD3) and T-cell subsets (CD4, CD8), and intercellular adhesion molecule-1 (ICAM-1) (CD54), and analysed their relation with the abnormal expression of ICAM-1 on proximal tubule epithelium in sequential renal sections from 48 patients with IgAN stratified according to the severity of the interstitial cellular infiltration observed by light microscopy. In IgAN without (n = 15) and with (n = 7) interstitial cellular infiltration of 1+, ICAM-1 expression on vascular endothelium was unchanged with respect to that observed in the normal kidney; the proximal tubule epithelium was negative for this stain. In IgAN with interstitial cellular infiltration of 2+ (n = 10), 3+ (n = 11), and 4+ (n = 5), ICAM-1+ stain was observed on the proximal tubule epithelium, the median value of its quantitative expression being 0.3, 0.1, and 0.2 (P = 0.0008), respectively. The tubular ICAM-1 + stain was significantly associated with the interstitial leucocytes identified by MA, and correlated with CD45+ (r = 0.59, P = 0.02), CD14+ (r = 0.54, P < 0.02), and CD3+ (r = 0.51, P = 0.02) interstitial leucocytes in IgAN with interstitial cellular infiltration. Interstitial ICAM-1+ and CD18+ leucocytes were correlated (r = 0.56, P < 0.001). Correlation was found between the quantitative tubular expression of ICAM-1+ and the number of CD45+ (r = 0.98, P < 0.0001), CD3+ (r = 0.48, P = 0.02), and CD8+ (r = 0.76, P < 0.02) glomerular leucocytes. Our results suggest that tubular and interstitial ICAM-1+ cells may participate in adhesive interactions with interstitial leucocytes. Interstitial T-cells and macrophages as well as glomerular T-cells bearing predominantly CD8+ phenotype could play a role in the induction of the tubular expression of ICAM-1 in IgAN.