Entactin: a possible auto-antigen in the pathogenesis of non-Goodpasture anti-GBM nephritis

It has recently been demonstrated that many patients with various types of glomerulonephritis have antibodies to the 6M guanidine-HCl extract of glomerular basement membrane (Bygren et al, Nephrol Dial Transplant 4:254-261, 1989). In the present study a 150 K protein was isolated from the guanidine extract of bovine glomerular basement membrane utilizing ion exchange and gel filtration chromatographic procedures. Amino acid analysis and size of the isolated protein revealed similarity to that of entactin/nidogen. The identity of this protein as entactin/nidogen was further suggested by its precipitation with two different antibodies in a radioimmunoassay and by its reaction with four different antibodies in a sandwich ELISA. Inhibition of the antibodies to 150 K by bovine entactin, which was isolated separately and sequenced for amino acids, confirmed the identity of the 150 K protein as entactin/nidogen. Furthermore, it was shown that about one third of those patients who show antibodies to the crude guanidine extract have circulating antibodies directed against entactin. This was further confirmed by the competitive inhibition of antibodies to the crude guanidine extract in one of the positive serum by entactin in an ELISA inhibition and by immunoblotting experiments. These observations propose entactin as a possible non-Goodpasture glomerular basement membrane antigen that could be involved in the pathogenesis of certain forms of autoimmune glomerulonephritis (non-Goodpasture anti-GBM glomerulonephritis) in man. Most of these patients have a granular pattern of the immunoglobulin deposition along the glomerular basement membrane. This suggests the possibility that anti-GBM glomerulonephritis in human beings can have non-linear immunoglobulin deposits along the GBM.