STUDIES OF BETA-LACTAM ANTIBIOTIC ALLERGY

IgE抗体介导的β-内酰胺类抗生素反应 （青霉素类、头孢菌素类、碳青霉烯类和单环内酰胺类） 这些药物常常使治疗复杂化， 严重限制其使用。 皮肤试验和体外特异性IgE 可以准确识别青霉素过敏患者的检测 已经制定，但有关的几个重要问题， 青霉素过敏仍未解决。 结构相似的 β-内酰胺抗生素，现在比 苄青霉素G给诊断带来了新的问题， 过敏反应的管理。 中描述的实验 这项建议涉及三个相关领域的基本问题， 人β-内酰胺类药物过敏的诊断与处理 青霉素过敏的体外检测和表征 IgE对头孢菌素的反应;以及头孢菌素的脱半抗原过程。 被β-内酰胺抗生素决定簇取代的蛋白质。 在 第一组实验，新的体外检测方法 的IgE t青霉素和常规青霉素皮肤试验将 用于澄清有关准确的 青霉素过敏的诊断 竞争可能的解释 将研究急性β-内酰胺类药物脱敏。 用β-内酰胺类药物治疗的患者的脱敏将 被探索。 第二组实验将研究IgE， 头孢菌素决定簇和由其他决定簇形成的决定簇 β-内酰胺类药物的体外分析方法。 头孢菌素与其他β-内酰胺类抗生素的交叉反应 决定因素将被衡量。 第三组实验 将表征人类蛋白质的脱半抗原化。 最近 研究已经揭示了人血浆和血清 去除与人硒共价连接的青霉素决定簇， 通过酰胺键和二硫键连接白蛋白。 这些活动将 特征及其与临床反应的关系 将对青霉素进行评估。 这些相互关联的研究将提供 新的一般方法和重要的新见解， β-内酰胺免疫化学、诊断和脱敏 药物过敏

IgE antibody mediated reactions to beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) frequently complicate therapy with these agents and impose a serious limitation on their use. Skin tests and in vitro specific IgE assays that can accurately identify penicillin allergic patients have been developed, but several important issues pertaining to penicillin allergy remain unresolved. The structurally similar beta-lactam antibiotics, now more widely used than benzylpenicillin G, impose new problems for diagnosis and management of allergic reactions. The experiments described in this proposal address fundamental issues in three related areas of human beta-lactam drug allergy: the diagnosis and management of penicillin allergy; the in vitro detection and characterization of IgE to cephalosporins; and the process of dehaptentation of proteins substituted with beta-lactam antibiotic determinants. In first group of experiments, new in vitro methods for the detection of IgE t penicillin and conventional penicillin skin tests will be used to clarify controversial issues pertaining to the accurate diagnosis of penicillin allergy. Competing possible explanations for acute beta-lactam drug desensitization will be investigated. Resensitization of patients treated with a beta-lactam drug will be explored. The second group of experiments will study IgE to cephalosporin determinants and determinants formed from other beta-lactam drugs using new in vitro assay methods. Crossreactivities among cephalosporin and other beta-lactam determinants will be measured. The third group of experiments will characterize dehaptenation of human proteins. Recent studies have disclosed the ability of human plasma and serum to remove penicillin determinants covalently attached to human se- albumin by amide and disulfide bonds. These activities will characterized and their relationship to clinical reactions to penicillin will be assessed. These interrelated studies will provide new general approaches and significant new insights into the immunochemistry, diagnosis, and desensitization of beta-lactam drug allergy.