Epitope targeting of the autoantibodies on the GM-CSF molecule. (A) Three-dimensional diagram of GM-CSF showing the 4 regions covered by the murine monoclonal antibodies used for epitope mapping of autoantibodies isolated from iPAP patients. Murine antibodies and the epitopes on human GM-CSF they recognize included 4117 (residues 1-11), 1089 (residues 40-77), 3092 (residues 78-94), and 1022 (residues 110-127), respectively. (B) Competitive GM-CSF binding assay of the autoantibodies with epitope-specific murine monoclonal antibodies. Each bar indicates the percentage of inhibition of [¹²⁵I]-GM-CSF binding to each monoclonal antibody by the autoantibodies from each patient with iPAP. Percentage of inhibition for the reactions without the autoantibodies and without monoclonal antibody was defined as 0% and 100% inhibition, respectively. Control human IgG and rabbit anti-GM-CSF peptide 54-73 polyclonal antibodies were used for negative and positive controls, respectively. Distribution of the percentage of inhibition was variable among the patients, but the autoantibodies consistently and strongly inhibited GM-CSF binding to the monoclonal antibody 3092.