Human monoclonal multiple-organ-reactive autoantibodies distinguished by mouse monoclonal anti-idiotypic antibodies: expression of idiotopes in humans with and without autoimmune diseases.

Previously we reported on the production and characteristics of a number of human monoclonal autoantibodies. All of these autoantibodies were of the IgM class and reacted with antigens in multiple organs. In this study we generated IgG murine monoclonal anti-idiotypic antibodies against five human monoclonal autoantibodies, (i.e., MOR-h2, MOR-h3, MOR-h4, CG1, and CG2). These anti-idiotypic antibodies reacted strongly with the corresponding human monoclonal autoantibody, but minimally or not at all with other human monoclonal autoantibodies. By using these anti-idiotypic antibodies as probes, we screened sera obtained from normal individuals and patients with insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and systemic lupus erythematosus for the expression of idiotopes. Our study showed that the idiotopes recognized by three of the anti-idiotypic antibodies, i.e., anti-CG1, anti-CG2, and anti-MOR-h2, were not expressed, but the idiotopes recognized by two of the anti-idiotypic antibodies, i.e., anti-MOR-h3 and anti-MOR-h4, were expressed in normal individuals. In patients with autoimmune disorders, there was no increase in the expression of the CG1, CG2, and MOR-h2 idiotopes, but 45 and 23% of the patients with systemic lupus erythematosus showed a significant increase in the expression of the MOR-h3 and MOR-h4 idiotopes respectively. These findings show that there is widespread expression in the B cell repertoire of certain autoantibody-associated idiotopes.