IMMUNOLOGIC REACTION TO INSULIN AND OTHER PROTEINS

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• 作者：Leslie C. Grammer ; MD^*
• 刊名：Immunology and Allergy Clinics of North America
• 出版年：1998
• 出版时间：1 November 1998
• 年：1998
• 卷：18
• 期：4
• 页码：809-816
• 全文大小：571 K

文摘

Most pharmacologic agents are small haptens (<1 kD) that require conjugation to a protein moiety to be recognized by the human immunologic system. This recognition may subsequently result in sensitization and hypersensitivity reactions. Pharmacologic agents that are proteins of molecular weight greater than 3 kD, either nonhuman or human recombinant, can be recognized by the human immunologic system and can cause sensitization and resultant hypersensitivity reactions. Therefore, these proteins can be used as skin testing allergens or as antigens in in vitro assays. Nonhuman, protein hormones like porcine insulin and adrenocorticotropic hormone (ACTH) are well recognized causes of hypersensitivity reactions. Nonhuman protein enzymes like streptokinase and chymopapain have been reported to cause hypersensitivity reactions. Antithymocyte globulin, produced from equine or rabbit immunoglobulin, is a well characterized cause of both immediate Type I hypersensitivity and Type III hypersensitivity.

It was somewhat unexpected that hypersensitivity reactions to human recombinant proteins occurred. It is speculated that these hypersensitivity reactions are caused by B-cell recognition of alterations in tertiary protein structure because the primary amino acid sequence, recognized by T cells, is identical to endogenously produced human proteins. The first recombinant human protein reported to elicit hypersensitivity reactions was insulin. Many of the patients who were initially described as allergic to human insulin had been sensitized by bovine or porcine insulin. Subsequently, administration of recombinant human proteins, including human insulin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and sI1-1rI, with no prior sensitization to nonhuman analogues, has been reported to cause hypersensitivity reactions.