Natural anti-GBM antibodies from normal human sera recognize alpha3(IV)NC1 restrictively and recognize the same epitopes as anti-GBM antibodies from patients with anti-GBM disease.

Anti-GBM disease is a rare autoimmune condition characterized by autoantibodies targeting the alpha3 chain non-collagen 1 domain of type IV collagen (alpha3(IV)NC1). Recently, we isolated IgG reacting with alpha3(IV)NC1 from normal healthy human sera. The current study examined the antigen and epitope specificity of these natural autoantibodies (NAA) using recombinant human alpha1, 3, 5(IV)NC1 and three constructs expressing, previously defined epitope regions designated E(A), E(B) and S2, in the alpha1(IV)NC1 background. The NAA preparations reacted with recombinant human alpha3(IV)NC1 to the same extent as with purified bovine alpha(IV)NC1, but not with recombinant human alpha1 and alpha5(IV)NC1. NAA preparations recognized the three chimeric proteins (E(A), E(B) and S2) yielding similar absorbance values. We conclude that anti-GBM NAA recognize the same major epitopes as anti-GBM antibodies from patients with Goodpasture's disease.