Dreborg S, Akerblom E B
Research and Development, Pharmacia Diagnostics AB, Uppsala, Sweden.
Crit Rev Ther Drug Carrier Syst. 1990;6(4):315-65.
On the basis of the results of experiments in naive mice, i.e., in mice which had not been presensitized, it was anticipated that mPEG-modified allergens would suppress the specific IgE response in allergic humans. However, only minor or no suppression of IgE antibodies was induced on administration of mPEG conjugates in allergic patients with a longstanding IgE response. This observation was later confirmed in pre-sensitized animals. The mPEG-modified allergens can be synthesized in a reproducible manner. This makes mPEG-modified allergens suitable for production and quality control. There is indirect evidence, i.e., identification of IgE and IgG antibody stimulation against all identified allergens, that the relevant determinants are available for processing by the immune system. By contrast, the polymerization of allergens by formaldehyde or glutaraldehyde leads to ill-defined, cross-linked high molecular weight materials. As in the case of other modified allergens, mPEG-modified allergens have been developed primarily because of their lower allergenicity than the original allergen preparations. However, they also retain clinical efficacy of the same magnitude as that induced by unmodified allergen preparations, which is a prerequisite for clinical use. IT with mPEG-modified pollen allergen preparations has been proven to be as effective as IT with unmodified allergens, when these preparations are given in similar doses. Furthermore, a more pronounced beneficial effect can be obtained with higher doses of mPEG-modified allergen, without the risk of side effects which are often precipitated by unmodified allergens. Therefore, it seems reasonable to suggest that children and young adults with developing sensitivity to perennial allergens, and without chronic changes of the bronchial mucosa, are the most suitable candidates for IT with mPEG-modified allergen preparations. Mite asthma, which always includes bronchial inflammation and nonspecific hyperresponsiveness, represents a more complicated model. In mite asthmatics mPEG-modified mite allergen preparations were safer than the corresponding unmodified preparation. Although bronchial sensitivity to allergen and histamine did not change significantly in mite asthmatics during the observation time, it appears that IT with mPEG-modified mite allergen led to a decrease in the releasability of histamine from skin mast cells, as measured by SPT, to a similar degree as observed in pollinosis patients. Therefore, it may be inferred that the allergic component of asthma might be influenced by IT with mPEG allergens. As a consequence, before the start of IT, the degree of reversibility of pathophysiological changes in the bronchial wall should be considered.(ABSTRACT TRUNCATED AT 400 WORDS)
基于对未预先致敏的新生小鼠所做的实验结果，预计甲氧基聚乙二醇（mPEG）修饰的变应原会抑制过敏人群中的特异性IgE反应。然而，在具有长期IgE反应的过敏患者中，给予mPEG偶联物后，仅诱导出轻微的IgE抗体抑制或未产生抑制。这一观察结果后来在预先致敏的动物中得到证实。mPEG修饰的变应原能够以可重复的方式合成。这使得mPEG修饰的变应原适用于生产和质量控制。有间接证据表明，即针对所有已鉴定的变应原鉴定出IgE和IgG抗体刺激，相关决定簇可被免疫系统处理。相比之下，用甲醛或戊二醛使变应原聚合会产生不明确的、交联的高分子量物质。与其他修饰的变应原一样，开发mPEG修饰的变应原主要是因为它们的致敏性低于原始变应原制剂。然而，它们也保留了与未修饰的变应原制剂相同程度的临床疗效，这是临床应用的前提条件。当以相似剂量给予时，经证实，用mPEG修饰的花粉变应原制剂进行免疫治疗（IT）与用未修饰的变应原进行IT一样有效。此外，给予更高剂量的mPEG修饰的变应原可获得更显著的有益效果，且无未修饰变应原常引发的副作用风险。因此，似乎有理由建议，对常年性变应原敏感性正在发展且支气管黏膜无慢性改变的儿童和年轻人，是用mPEG修饰的变应原制剂进行IT的最合适人选。螨性哮喘总是包括支气管炎症和非特异性高反应性，是一个更复杂的模型。在螨性哮喘患者中，mPEG修饰的螨变应原制剂比相应的未修饰制剂更安全。尽管在观察期内螨性哮喘患者对变应原和组胺的支气管敏感性没有显著变化，但似乎用mPEG修饰的螨变应原进行IT可使皮肤点刺试验（SPT）测量的皮肤肥大细胞组胺释放能力降低，程度与花粉症患者中观察到的相似。因此，可以推断哮喘的过敏成分可能会受到用mPEG变应原进行IT的影响。因此，在开始IT之前，应考虑支气管壁病理生理变化的可逆程度。（摘要截短至400字）
