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免疫缺陷病毒性胃肠炎患者口服人血清免疫球蛋白:药代动力学与功能分析

Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis. A pharmacokinetic and functional analysis.

作者信息

Losonsky G A, Johnson J P, Winkelstein J A, Yolken R H

出版信息

J Clin Invest. 1985 Dec;76(6):2362-7. doi: 10.1172/JCI112248.

Abstract

We examined the pharmacokinetics and immunological activity of human serum immunoglobulins (HSG) possessing anti-rota-virus activity which were orally administered to three children with primary immunodeficiency syndromes and prolonged gastrointestinal excretion of rotavirus. Detailed analysis of the excretion of immunoglobulins labeled with biotin or I125 revealed that approximately 50% of the recovered radioactivity was excreted in the stools over a 3-d period. Approximately half of the excreted radioactivity recovered in the stool was in a macromolecular form with immunological activity. The remainder of the recovered radioactivity was excreted in the urine as low molecular weight fragments or free iodide. In addition, immunological and chromatographic analyses revealed that the oral administration of HSG resulted in the generation of rotavirus-specific immune complexes in the gastrointestinal tract with a subsequent decrease in the presence of uncomplexed rotavirus antigen. These studies indicate that orally administered HSG can survive passage in the gastrointestinal tract in an immunologically active form, and that the oral administration of immunoglobulins with specific reactivities has potential for the prevention or treatment of gastrointestinal infections.

摘要

我们研究了具有抗轮状病毒活性的人血清免疫球蛋白(HSG)的药代动力学和免疫活性,该免疫球蛋白口服给予了三名患有原发性免疫缺陷综合征且轮状病毒在胃肠道排泄时间延长的儿童。对用生物素或I125标记的免疫球蛋白排泄情况的详细分析表明,在3天的时间里,约50%回收的放射性物质经粪便排出。粪便中回收的排泄放射性物质约一半呈具有免疫活性的大分子形式。其余回收的放射性物质以低分子量片段或游离碘化物的形式经尿液排出。此外,免疫和色谱分析表明,口服HSG导致胃肠道中产生轮状病毒特异性免疫复合物,随后未结合的轮状病毒抗原数量减少。这些研究表明,口服的HSG能够以免疫活性形式在胃肠道中存活,并且口服具有特定反应性的免疫球蛋白具有预防或治疗胃肠道感染的潜力。

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