SELECTION OF AN RNA MOLECULE THAT MIMICS A MAJOR AUTOANTIGENIC EPITOPE OF HUMAN INSULIN-RECEPTOR

Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind spe cifically to autoantibodies and inhibit their interaction with the tar get antigen. Here we report the identification of an RNA sequence that binds a mouse monoclonal antibody specific for an autoantigenic epito pe of human insulin receptor. The RNA ligand binds specifically and wi th high affinity (apparent Kd similar or equal to 2 nM) to the anti-in sulin receptor antibody and not to other mouse IgGs. The RNA can also act as a decoy, blocking the antibody from binding the insulin recepto r. Thus, it probably binds near the combining site on the antibody. St rikingly, the RNA cross-reacts with autoantibodies from patients with extreme insulin resistance. One simple explanation is that the selecte d RNA may structurally mimic the antigenic epitope on the insulin rece ptor protein. These results suggest that decoy RNAs may be useful in t he treatment of autoimmune diseases.