Characterization of purified autoantibodies to the insulin receptor from six patients with type B insulin resistance.

Anti-insulin-receptor autoantibodies are present in the serum of patients with the type B syndrome of extreme insulin resistance. Sera from six patients with this syndrome were purified over protein-A agarose to remove insulin and other serum factors and obtain an immunoglobulin fraction. These purified fractions were used to quantitatively determine the antibodies' activity in three separate assays. The ability to inhibit insulin binding was determined in an assay using fibroblasts that overexpress the human insulin receptor; the ability to immunoprecipitate the receptor was determined in an assay using biosynthetically labeled insulin receptors rather than insulin cross-linked receptors; and the ability to stimulate glucose oxidation was determined in isolated adipocytes. We show that the ability of these antibodies to inhibit insulin binding is tightly coupled to their ability to immunoprecipitate the biosynthetically labeled receptor, but neither assay predicts the bioactivity of these immunoglobulins. We suggest that the inability to show this tight coupling in the past may be due to methodological differences. We find no evidence that these antibodies are anti-idiotypic antibodies.