Multiple organ-reactive IgG antibody induced by an antiidiotypic antibody to a human monoclonal IgM autoantibody.
MOR-h1 is a human multiple organ-reactive (MOR) monoclonal autoantibody (Ab1) that reacts with human growth hormone (hGH) and a 35 kD protein found in the anterior pituitary, thyroid, stomach, and pancreas. 4E6 is a mouse monoclonal anti-idiotypic antibody (Ab2) that reacts with the paratope of MOR-h1 and is ligand inhibitable. In the present study, we immunized a rabbit with 4E6 and purified an IgG fraction (anti-4E6) from the sera. Competitive inhibition experiments showed that anti-4E6 (Ab3) binds to the same epitope on 4E6 and to the same antigens (i.e., hGH and 35 kD protein) as does MOR-h1. By immunofluorescence, anti-4E6, an IgG antibody, shows the same multiple organ reactivity with tissues as does MOR-h1, an IgM antibody. From these and other studies, we conclude that the 4E6 paratope (Ab2) has a conformational resemblance to an epitope on hGH and the 35 kD protein. This raises the possibility that antibodies made in response to certain anti-idiotypic antibodies may be one of the mechanisms for triggering an autoimmune response.
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D013006:Growth Hormone / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D014018:Tissue Distribution
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D013006:Growth Hormone