[Cellular pathology of Heyman nephritis: monoclonal antibodies against the pathogenic antigen Gp 330].

Heymann nephritis is an experimental auto-immune glomerulonephritis, closely resembling human epimembranous nephritis, which is induced by identified antigens in the brush border membranes of kidney proximal tubules. The hallmark of the disease is the accumulation of immune deposits in a granular pattern in the lamina rara externa of the glomerular basement membrane. We have established that a large membrane glycoprotein with an apparent molecular weight of 330 kDal (pg 330) is the pathogenic antigen. By means of immunohistochemistry, using mono- and polyclonal anti-pg 330 IgG we found that gp 330 is present in the cell membranes of glomerular epithelial cells and that it is concentrated there in coated pits (specialized areas off the cell membrane which play a key role in receptor mediated endocytosis for ligands such as insulin and others). On the basis of these findings we propose the following mechanism of formation of an immune deposit: (1) "In-situ" formation of immune complexes of gp 330 and anti-gp 330 IgG; (2) shedding of the immune complexes into the basement membrane and (3) crosslinking of the immune complexes into the basement membrane. This scheme could be a general mechanism by which immune deposits are formed also in various other auto-immune diseases.