TUMOR-NECROSIS-FACTOR-ALPHA IS EXPRESSED BY GLOMERULAR VISCERAL EPITHELIAL-CELLS IN HUMAN MEMBRANOUS NEPHROPATHY

The role of tumor necrosis factor alpha (TNF-alpha) was examined in bi opsy-proven glomerulonephritis by immunohistochemistry, in situ hybrid ization, immunogold electron microscopy, immunoassay in serum and urin e, and urinary immunoblot. Striking glomerular capillary wall and visc eral glomerular epithelial cell TNF-alpha protein staining was observe d in all cases of membranous nephropathy and membranous lupus nephropa thy. Staining was less frequently observed in crescentic glomeruloneph ritis and in isolated cases of other histological subtypes of glomerul onephritis, usually in association with glomerular macrophages. By imm unogold electron microscopy TNF-alpha was localized in membranous neph ropathy within the visceral glomerular epithelial cells, and also ill the glomerular basement membrane, especially in relation to immune dep osits. In situ hybridization localized TNF-alpha mRNA exclusively to g lomerular epithelial cells in all biopsies with membranous morphology but not in other histological subtypes. Concentrations Of TNF-alpha we re significantly increased compared with normal controls in the urine of patients with membranous nephropathy and with crescentic glomerulon ephritis. The expression of TNF-alpha by glomerular epithelial cells e xclusively and universally in biopsies showing a membranous morphology strongly suggests this cytokine has a role in the pathogenesis of mem branous nephropathy.