LEUKOCYTE INFILTRATION AND INTERCELLULAR-ADHESION MOLECULE-1-MEDIATEDCELL-INTERACTIONS IN IMMUNOGLOBULIN-A NEPHROPATHY

Background.-Mononuclear leukocytes have a role in immunoglobulin (Ig) A nephropathy. Renal leukocyte recruitment is mediated by adhesive int eractions between leukocytes and their ligands on renal cells. Methods .-We assessed interstitial and glomerular leukocytes using an avidin-b iotin-peroxidase method with monoclonal antibodies (MAbs) against leuk ocytes (CD45), beta 2-integrin (CD18), macrophages (CD14), T cells (CD 3) and T-cell subsets (CD4, CD8), intercellular adhesion molecule-1 (I CAM-1) (CD54), and HLA class II antigens. We analyzed their relation w ith the abnormal expression of ICAM-1 on proximal tubular epithelium i n sequential renal sections from 57 patients with IgA nephropathy stra tified by degrees of interstitial cellular infiltration as seen by lig ht microscopy. Results.-In IgA nephropathy without infiltration (n = 1 5) and with interstitial cellular infiltration of 1+ by light microsco py (n = 11), ICAM-1 expression on vascular endothelium was unchanged w ith respect to that observed in the normal kidney; the proximal tubula r epithelium was negative for this stain. Moreover, in IgA nephropathy with interstitial cellular infiltration greater than or equal to 2+ b y light microscopy (n = 31), ICAM-1(+) stain was seen on proximal tubu lar epithelium. The value of ICAM-1(+) tubule staining was significant ly (P = .0004) higher in the biopsies with a higher degree of intersti tial cellular infiltration seen by light microscopy. The tubular ICAM- 1(+) stain was significantly associated with the number of interstitia l leukocytes identified by the MAbs tested and correlated (P < .05) wi th CD45(+) (r = 0.59), CD14(+) (r = 0.54), and CD3(+) (r = 0.51) inter stitial leukocytes in IgA nephropathy with interstitial cellular infil tration by light microscopy. Interstitial ICAM-1(+) cells and intersti tial CD18(+) leukocytes were correlated (r = 0.85, P < .001). Correlat ion was found between the value of ICAM-1(+) tubule staining and the n umber of CD45(+) (r = 0.87, P < .01), CD14(+) (0.58, P <.05), and CD8( +) (r = 0.68, P < .05) glomerular leukocytes. Conclusions.-Our results suggest that tubular and interstitial ICAM-1(+) cells may participate in adhesive interactions with interstitial leukocytes. Epithelial tub ular cells expressing ICAM-1 may be a marker of tubulointerstitial dis turbance upregulated by interstitial and glomerular infiltration of ma crophages and T cells in IgA nephropathy.