Journal of Clinical Endocrinology & Metabolism, Vol 61, 986-989, Copyright © 1985 by Endocrine Society

ARTICLES

Human autoantibodies directed against the human, but not the rat, insulin receptor

R De Pirro, L Rossetti, A Montemurro, R Lauro, S Gammeltoft, BA Maddux and ID Goldfine

Prior studies with monoclonal antibodies produced against the human insulin receptor in mice revealed that these antibodies may be species specific. Whether species-specific antibodies to the insulin receptor occur spontaneously in patients, however, has not been previously investigated. Recently, we found that the serum immunoglobulin G from a patient with lupus nephritis, insulin resistance, and hypoglycemia contained multiple subpopulations of antibodies directed at the human insulin receptor. We report herein that one such subpopulation has a high affinity for the human insulin receptor. This antibody subpopulation at 10 nM half-maximally inhibited [125I]insulin binding to human IM-9 lymphocytes, circulating erythrocytes and monocytes, isolated adipocytes, and placenta membranes. In contrast, this antibody subpopulation did not inhibit [125I]insulin binding to isolated rat adipocytes and hepatocytes, even at concentrations as high as 100 nM. These studies indicate that species-specific antibodies can occur spontaneously in patients with antiinsulin receptor antibodies.