Study on the change of glomerular antigenicity in various renal diseases with anti-human renal monoclonal antibodies

Abstract

We produced 22 different kinds of monoclonal antibody (Mab) by immunizing mice with human GBM antigens. In these Mabs, Mab-G1 to G5 recognized only GBM in the glomerulas, Mab-E1 and E2 recognized only glomerular epithelial cells, and Mab-M1 to M4 recognized mainly mesangium. The reactions of these Mabs with known GBM antigens such as type IV collagen, fibronectin and laminin were negative by immunoblotting. Using Mab-G1, Mab-E1 and Mab-M1, changes in the antigenicity of antigens recognized by Mabs were examined on kidney sections from the patients with various renal diseases by the indirect immunofluorescence test. When Mab-G1 recognizing GBM was used, there was no particular change of anti-genicity in minimal change nephrotic syndrome (MCNS) and IgA nephropathy (IgA), whereas in membranous nephropathy (MN) thickened GBM was found to maintain anti-genicity and the region of deposits was observed as negative punched-out region. In type I and III of membranoproliferative glomerulonephritis (MPGN), GBM was observed only outside of subendothlial deposits without showing double contour. In type II MPGN, GBM showed a double linear pattern and antigenicity of GBM in regions of dense deposits was not detected. When Mab-E1 recognizing glomerular epithelial cells was used, there was no change of antigenicity in the renal diseases. Further, in crescentic glomerulone-phritis, the region of the cellular crescents was not stained, When Mab-M1 recognizing mesangium was used, extensive staining was observed in the increased mesangium in IgA, MPGN, and diabetic nephropathy. We feel that it is of significance in elucidating the pathogenesis of renal diseases to study the changes of glomerular antigenicity in diseased kidneys by using anti-human renal monoclonal antibodies.