Hubbard A K, Levy J P, Roth T P, Gandolfi A J
Department of Anesthesiology, University of Arizona, Tucson 85724.
Drug Chem Toxicol. 1990;13(2-3):93-112. doi: 10.3109/01480549009018115.
Four hapten-carrier conjugates were synthesized to evaluate any potential antigenic similarities between these synthetic compounds and the immunogens induced in vivo by the anesthetic, halothane and, thus, be used eventually as a more sensitive probe to detect the presence of these halothane-induced antibodies in halothane-exposed individuals. In this study, antibodies from five halothane hepatitis patients were used to evaluate these antigenic alterations since the specificity of these antibodies would most accurately reflect the antigenic structure of halothane-induced immunogens. Quantitation of antibody binding to these synthetic proteins was determined in an enzyme linked immunosorbent assay and immunoblot techniques. Trifluoroacetylated rabbit serum albumin was 5 times more reactive with these antibodies and thus more antigenic than the homologous acetylated moiety confirming the importance of the trifluoromethyl moiety as an epitope in the immunogen in vivo. Insertion of a spacer arm, aminocaproic acid, between the hapten and carrier moieties and an epitope density of 40% acetylation also increased antigenicity. Through these structural alterations produced in vitro, antigenic compounds have been produced which may resemble more closely the immunogen elicited in vivo and which may ultimately serve as more sensitive probes for halothane-induced antibodies from exposed individuals.
合成了四种半抗原-载体缀合物，以评估这些合成化合物与麻醉剂氟烷在体内诱导产生的免疫原之间是否存在潜在的抗原相似性，从而最终用作更灵敏的探针，以检测接触氟烷个体中这些氟烷诱导抗体的存在。在本研究中，使用了五名氟烷性肝炎患者的抗体来评估这些抗原改变，因为这些抗体的特异性将最准确地反映氟烷诱导免疫原的抗原结构。通过酶联免疫吸附测定和免疫印迹技术测定抗体与这些合成蛋白的结合定量。三氟乙酰化兔血清白蛋白与这些抗体的反应性比同源乙酰化部分高5倍，因此抗原性更强，这证实了三氟甲基部分作为体内免疫原表位的重要性。在半抗原和载体部分之间插入间隔臂氨基己酸以及40%乙酰化的表位密度也增加了抗原性。通过体外产生的这些结构改变，已产生了可能更类似于体内诱导产生的免疫原的抗原化合物，这些化合物最终可能用作更灵敏的探针，用于检测接触个体中氟烷诱导的抗体。
