IMMUNOLOGICAL ANALYSIS OF SULFONAMIDE HYPERSENSITIVITY

药物的免疫病理反应是一种重要的免疫疾病 同时，也为人类研究提供了宝贵的机会 对生化定义的免疫反应和免疫病理反应 抗原。这个实验室最近的实验证明 抗N4-磺胺甲恶唑决定簇的免疫球蛋白、免疫球蛋白、免疫球蛋白和免疫球蛋白A抗体 在许多经历过不良反应的人身上都能检测到 在使用磺胺甲恶唑(SMX)治疗期间。该计划的目标 拟议的实验是为了系统地表征人类的免疫系统 对N4-磺胺甲恶唑基半抗原的反应并确定其作用 这些反应在临床上对SMX的不良反应各不相同。五 将进行一组实验。第一部分将探讨 假设细胞内形成的反应性代谢物或SMX 在大肠杆菌中表达适当的氧化酶、半抗原特异性蛋白 同一细胞在蛋白质合成或分泌过程中。分析 培养的细胞暴露于SMX和循环半抗原细胞和 在经过治疗的人类中，蛋白质将被执行。第二组 研究将扩展这些初步实验，并将测试 免疫病理反应的发生和表达假说 对SMX的反应与个体的乙酰化能力有关 在N4位给药物充氧。第三组研究将 解决了检测到的免疫反应是半抗原的假设 具有特异性，不受特定大分子载体的影响。十字 将研究由其他磺胺类化合物形成的N4-半抗原之间的反应 并将研究系统半抗原抑制的可能性。 第四组研究将评估特定抗体和淋巴细胞 使用SMX治疗后的反应以检验免疫假说 对SMX的反应是许多临床不良反应的基础 反应。特异性免疫应答与特异性免疫反应的关系 将探索临床现象。最后，一个持续的皮肤模型 药物过敏将被开发、分析并用作人类的模型 混合免疫病理学。从所述研究中获得的数据 应该会对半衰期的机制提供有价值的新见解， 人类免疫反应和免疫病理学。

Immunopathological reactions to drugs are important immunologic diseases and, at the same time, offer valuable opportunities to investigate human immune responses and immunopathologic reactions to biochemically defined antigens. Recent experiments in this laboratory have demonstrated that IgE, IgM, IgG, and IgA antibodies to the N4-sulfamethoxazoyl determinant are detectable in many individuals who have experienced adverse reactions during therapy with sulfamethoxazole (SMX). The objectives of the proposed experiments are to systematically characterize human immune responses to the N4-sulfamethoxazoyl hapten and to determine the role of these responses in the diverse clinical adverse reactions to SMX. Five groups of experiments will be performed. The first will explore the hypothesis that reactive metabolites or SMX, formed within a cell expressing appropriate oxidative enzymes, haptenate specific proteins in the same cell during protein synthesis or secretion. Analysis of cultured cells exposed to SMX and of circulating haptenated cells and proteins in treated humans will be performed. The second group of studies will extend these initial experiments and will test the hypothesis that haptenation and expression of immunopathologic reactions to SMX are related to an individual's ability to acetylate versus oxygenate the drug at the N4 site. The third group of studies will address the hypothesis that the immune responses detected are hapten specific and not influenced by specific macromolecular carriers. Cross reactions among N4-haptens formed from other sulfonamides will be studied and the potential for systemic hapten inhibition will be investigated. The fourth group of studies will assess specific antibody and lymphocyte responses following treatment with SMX to test the hypothesis that immune responses to SMX are the basis for many of the clinical adverse reactions. The relationship of specific immune responses to specific clinical phenomena will be explored. Finally, a skin model of sustained drug allergy will be developed, analyzed and used as a model of human mixed immunopathology. the data obtained from the described studies should provide valuable new insights into the mechanisms of haptenation, human immune responses, and immunopathology.