IMMUNOLOGICAL ANALYSIS OF SULFONAMIDE HYPERSENSITIVITY

药物免疫病理反应是重要的免疫性疾病 与此同时，也为研究人类的行为提供了宝贵的机会。 免疫应答和免疫病理学反应， 抗原 该实验室最近的实验表明， 针对N4-磺胺甲恶唑决定簇的IgE、IgM、IgG和伊加抗体 在许多经历过不良反应的个体中可检测到 磺胺甲恶唑（SMX）治疗期间。 的目标 拟议的实验是系统地表征人类免疫 对N4-磺胺甲恶唑半抗原的反应，并确定 这些反应在SMX的各种临床不良反应中。 五 将进行多组实验。 第一部分将探讨 假设反应性代谢物或SMX，在细胞内形成 表达适当的氧化酶，半抗原特异性蛋白， 在蛋白质合成或分泌过程中相同的细胞。 分析 暴露于SMX的培养细胞和循环半抗原化细胞， 将在治疗的人中进行蛋白质。 第二组 研究将扩展这些初步实验，并将测试 免疫病理反应半抗原化和表达假说 SMX与个体乙酰化能力有关， 在N4位点上抑制药物。 第三组研究将 解决检测到的免疫应答是半抗原的假设 特异性和不受特定大分子载体的影响。 横 将研究由其他磺胺形成的N4-半抗原之间的反应 并研究系统性半抗原抑制的潜力。 第四组研究将评估特异性抗体和淋巴细胞 SMX治疗后的反应，以检验免疫 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 将探讨临床现象。 最后，皮肤模型的持续 药物过敏将被开发，分析和用作人类的模型 混合免疫病理学 从所述研究中获得的数据 应该为半抗原化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.