ANTIBODIES AGAINST POLYETHYLENE-GLYCOL PRODUCED IN ANIMALS BY IMMUNIZATION WITH MONOMETHOXY POLYETHYLENE-GLYCOL MODIFIED PROTEINS
ANTIBODIES AGAINST POLYETHYLENE-GLYCOL PRODUCED IN ANIMALS BY IMMUNIZATION WITH MONOMETHOXY POLYETHYLENE-GLYCOL MODIFIED PROTEINS
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DOI：
10.1159/000233309
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
AKERBLOM, E
中科院分区：
文献类型：
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作者：
RICHTER, AW;AKERBLOM, E
用单甲氧基聚乙二醇化卵清蛋白、牛超氧化物歧化酶和豚草花粉提取液免疫兔，制备了兔抗聚乙二醇全佐剂抗体。免疫原性取决于蛋白质的性质和修饰程度。用修饰的OA，在FCA存在的情况下，大多数动物都表现出抗聚乙二醇的反应。使用修饰的SOD和RAG，只有一小部分动物有反应。在没有FCA的情况下，皮下注射修饰的OA不能在兔体内引起任何抗-PEG抗体反应，在小鼠中仅能产生微弱的反应。FCA给药的聚乙二醇10,000和100,000对兔无免疫原性，聚乙二醇5.9倍。106，给定S.C.对小鼠无免疫原性或免疫原性很差。用凝胶扩散法、异种被动过敏反应和被动血凝试验证明抗-聚乙二醇抗体被提高到聚乙二醇化修饰的蛋白质上。通过半抗原抑制沉淀法、被动血凝抑制法和交叉反应试验证实其特异性。分子量为4000的聚乙二醇酯能产生特定的沉淀物，小分子充当单价半抗原。从分子量为300的聚乙二醇半抗原抑制沉淀的结果来看，聚乙二醇的抗原决定簇可能是一个6-7-CH2CH2O-单位的序列。抗聚乙二醇单抗可用于分析。通过凝胶扩散法检测到聚乙二醇乙二醇酯的最低浓度为0.1-1微克/毫升。这些发现与人类使用聚乙二醇酶和过敏原治疗的临床相关性仍有待确定。
Antibodies to polyethylene glycol (PEG) were raised in rabbits by immunization with monomethoxy polyethylene glycol modified ovalbumin (OA), bovine superoxide dismutase (SOD) and ragweed pollen extract (Rag), given in Freund''s complete adjuvant (FCA). Immunogenicity depended on the nature of the protein and the degree of modification. With modified OA, in the presence of FCA, the majority of animals showed an anti-PEG response. With modified SOD and Rag only a small proportion of animals responded. In the absence of FCA, modified OA, given s.c., did not elicit any anti-PEG antibody response in rabbits and only a weak response in mice. PEG of MW 10,000 and 100,000 given in FCA was found nonimmunogenic in rabbits, and PEG of MW 5.9 .times. 106, given s.c. to mice, showed no or very poor immunogenic properties. Gel diffusion, heterologous passive anaphylaxis and passive hemagglutination were used to demonstrate anti-PEG antibodies raised to PEG-modified proteins. Specificity was confirmed by hapten inhibition of precipitation, inhibition of passive hemagglutination and cross-reactivity tests. PEG of MW = 4,000 produced specific precipitates, smaller molecules acted as monovalent haptens. From hapten inhibition of precipitation by PEG of MW 300 it appears that the antigenic determinant of PEG may be a sequence of 6-7 -CH2CH2O-units. Anti-PEG antibodies can be used analytically. By gel diffusion, Peg was detected in minimal concentrations of 0.1-1 .mu.g/ml. The clinical relevance of these findings with regard to therapy with PEG-modified enzymes and allergens in humans remains to be established.