Natural anti-GBM antibodies from normal human sera recognize α3(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 α3 chain non-collagen 1 domain of type IV collagen (α3(IV)NC1). Recently, we isolated IgG reacting with α3(IV)NC1 from normal healthy human sera. The current study examined the antigen and epitope specificity of these natural autoantibodies (NAA) using recombinant human α1, 3, 5(IV)NC1 and three constructs expressing, previously defined epitope regions designated EA, EB and S2, in the α1(IV)NC1 background. The NAA preparations reacted with recombinant human α3(IV)NC1 to the same extent as with purified bovine α(IV)NC1, but not with recombinant human α1 and α5(IV)NC1. NAA preparations recognized the three chimeric proteins (EA, EB 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.