Induction of antibodies to nuclear antigens in rabbits by immunization with hydralazine-human serum albumin conjugates.
Induction of antibodies to nuclear antigens in rabbits by immunization with hydralazine-human serum albumin conjugates.
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通过用肼苯哒嗪-人血清白蛋白缀合物免疫诱导兔子体内针对核抗原的抗体。
DOI：
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发表时间：
1975
影响因子：
15.9
通讯作者：
E. Hess
中科院分区：
文献类型：
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作者：
Y. Yamauchi;A. Litwin;L. Adams;H. Zimmer;E. Hess
抗高血压药物肼可在人体内诱发类似于自发性系统性红斑狼疮(SLE)的综合征。这种药物诱导综合征的发病机制尚不清楚。本研究共分5组：I组10只兔，在完全弗氏佐剂(CFA)中加入人血清白蛋白(HSA)进行高免疫；II组4只CFA中HSA免疫；III组4只CFA单独免疫；IV组5只联用兔血清白蛋白(RSA)；用肼丙嗪-人血清白蛋白免疫的兔子，其抗体效价升高，对单链DNA和天然DNA的抗体数量也逐渐增加。通过DNA结合抑制试验和DNA血凝试验确定抗DNA抗体与呋喃西林发生交叉反应。用该代谢物-人血清白蛋白化合物免疫的兔也得到了类似的结果，但主要的半抗原抗体反应是对该代谢物的。该组中的DNA抗体也能够被代谢物-HSA以及肼-HSA吸收，表明肼与其代谢物之间存在交叉反应。用肼丙嗪-RSA免疫使兔子产生对肼的抗体，但不产生对DNA的抗体，这表明需要对载体蛋白的免疫反应才能产生与DNA反应的抗体。因此，用肼丙嗪-蛋白质结合物对兔进行超量免疫可提供一种有用的系统性红斑狼疮动物模型。这些数据表明，对肼类药物的免疫反应可能在人类肼类药物诱发的系统性红斑狼疮中起重要作用。
The antihypertensive drug hydralazine can induce in man a syndrome similar to spontaneous systemic lupus erythematosus (SLE). The pathogenesis of this drug-induced syndrome is not understood. In this investigation, five groups of rabbits were studied: group I, 10 rabbits hyperimmunized with hydralazine conjugated to human serum albumin (HSA) in complete Freund's adjuvant (CFA); group II, four rabbits with HSA in CFA; group III, four rabbits with CFA alone; group IV, five rabbits with hydralazine conjugated to rabbit serum albumin (RSA); and group V, four rabbits with a major metabolite of hydralazine conjugated to HSA. The rabbits immunized with hydralazine-HSA developed rising titers of antibodies to hydralazine and progressively increasing amounts of antibodies to both single-stranded and native DNA. The antibodies to DNA were cross-reactive with hydralazine as determined by inhibition of DNA binding and DNA hemagglutination tests. Similar results were obtained in rabbits immunized with the metabolite-HSA compound except the major hapten antibody response was to the metabolite. The DNA antibodies in this group were also capable of being absorbed by metabolite-HSA as well as hydralazine-HSA, indicative of the cross-reactivity between hydralazine and its metabolite. Immunization with hydralazine-RSA caused rabbits to produce antibodies to hydralazine but not to DNA, indicating the requirement for an immune response to the carrier protein in order for antibodies reactive with DNA to be produced. Thus, hyperimmunization of rabbits with hydralazine-protein conjugates may provide a useful animal model of SLE. The data suggests that an immune response to hydralazine may be important in human hydralazine-induced SLE.