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

Background. 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. Methods. 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. Results. 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. Conclusions. 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.