Immunologic Tolerance to Intravenously Injected Insulin

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Abstract
Rosalyn Yalow, the inventor of radioimmunoassay, found that insulin treatments led to the production of antibodies against insulin.1 Initially, this phenomenon was thought to be due to slight immunogenicity induced by the refining of preparations or the difference in amino acid sequences between species. However, even today, when genetically engineered preparations of human insulin are used, anti–human insulin IgG subclasses still are frequently detected in patients treated with insulin. Why therapeutically used insulin molecules, despite having exactly the same primary structure as endogenous insulin, are immunogenic has not been fully clarified.