IDENTIFICATION OF NEW GLOMERULAR PROGRESSION FACTORS USING MONOCLONAL ANTIBODY

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In order to identify a new cell surface antigen as a potential marker of renal glomerular cell injury, we produced a monoclonal antibody (Mab), 1F3, by immunizing mice with cultured human glomerular cells. Immunohistochemical studies demonstraated that 1F3 recognizing molecule (1F3 molecule) was strongly expressed on the cell surface of glomerular podocytes and very weakly on parietal epithelial cells in the normal kidney. Immunoprecipitation revealed that 1F3 recognized a 125 KDa protein under reducing conditions. Sequenced N-terminal amino acid analysis following 1F3 immunoaffinity purification indicated that 1F3 molecule resembled integrin alpha3 subunit. Biopsy specimens from patients with a variety of glomerular and tubulointerstitial diseases showed that 1F3 antigen was almost negative in cellular crescents but was strongly expressed in fibro-cellular crescents. 1F3 antigen became positive in atrophic tubules that were seen in diseased kidneys. Severity of tubular atrophy correlated well with the extent of tubular expression of 1F3 antigen. Urine examination using ELISA showed that increased excretion of 1F3 molecule was observed in the patients with glomerulonephritis as compared with healthy donor. These results indicate that Mab, 1F3 marks cell biological changes of renal epithelial cells under disease conditions and may be a useful marker for progressive kidney diseases.