Antibodies to Insulin Receptor Followed by Anti-Idiotype: Antibodies to Insulin in Child With Hypoglycemia

A child presenting severe hypoglycemia despite low or normal secretion of insulin was found to have IgM antibodies to the insulin receptor. These antibodies stimulated lipogenesis in fat cells in vitro and competed with insulin for binding to insulin receptors. After treatment with glucocorticoids, the anti-receptor antibodies and the hypoglycemia both disappeared, and antibodies to insulin appeared in the patient's serum. The anti-insulin antibodies were isolated by affinity chromatography and were found to inhibit the antiinsulin- receptor antibodies that were present earlier. The interaction between the patient's anti-insulin antibodies and his anti-receptor antibodies suggests that these two species of antibodies are related as idiotypes and anti-idiotypes. We also studied the interaction of the hypoglycemic patient's anti-receptor antibodies with anti-insulin antibodies of a diabetic patient and with anti-insulin antibodies of mice immunized to insulin. The hypoglycemic patient's antireceptor antibodies were neutralized by the diabetic patient's anti-insulin antibodies, indicating that antiinsulin antibodies with a common idiotype may arise in both diabetes and hypoglycemia. Moreover, mouse anti-insulin antibodies that interacted with mouse antireceptor antibodies neutralized the hypoglycemic patient's anti-receptor antibodies. In contrast, mouse anti-insulin antibodies that did not interact with the mouse anti-receptor antibodies did not neutralize the hypoglycemic patient's anti-receptor antibodies. Thus, the human anti-insulin antibodies share an idiotype with a specific class of mouse anti-insulin antibodies. These findings lead to three conclusions: 7) hypoglycemia of young children can be associated with anti-insulin-receptor antibodies, 2) the anti-idiotypic network may operate in humans to generate autoantibodies to a hormone, and 3) mice and humans can generate networks with common idiotypes.