Zhao Z, Baldo B A, Rimmer J
Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, St Leonards, Australia.
Clin Exp Allergy. 2002 Nov;32(11):1644-50. doi: 10.1046/j.1365-2222.2002.01492.x.
An appreciation of the structural heterogeneity of allergenic determinants on penicillins and cephalosporins reveals the importance of side-chain groups and their involvement in many allergies to beta-lactam drugs. Although allergenic cross-reactions between penicillins and cephalosporins are known to occur, the precise molecular bases of such recognitions and cross-sensitivities have rarely been studied and identified.
The unexpected finding of a high incidence of positive IgE antibody reactions with both benzylpenicillin and cephalothin prompted serological and immunochemical studies to identify the chemical basis of antibody recognition of these drugs from the two different families of beta-lactam antibiotics.
Adsorption studies were employed to identify whether or not a single population of antibodies was involved in the recognition of benzylpenicillin and cephalothin. Identification of the fine structural features recognized by IgE antibodies was investigated by quantitative hapten inhibition studies employing carefully selected beta-lactam drugs, analogues and some other structurally related chemicals.
Adsorption studies with penicilloic acid-solid phase clearly established that a single population of cross-reacting antibodies recognized both benzylpenicillin and cephalothin. Quantitative inhibition findings, especially with phenylacetic acid and 2-thiopheneacetic acid and with cephaloridine and cefoxitin, which have the same (2-thienyl)methyl side-chain as cephalothin, implicated the methylene group as the focus of the allergenic determinant recognized on benzylpenicillin and cephalothin. In addition to the methylene group, recognition graded into neighbouring structures including the amide group and extended weakly to the beta-lactam ring.
Results confirmed that structural features as small as a methylene group may be allergenically important. In the present case, this group, making up only part of the different side-chains on benzylpenicillin and cephalothin, together with neighbouring structures extending toward the beta-lactam ring, accounted for the cross-reactivity seen between structures that, at first sight, appear to be not closely related. Such subtle, small, common structural features are likely to be immunologically recognized and implicated in allergic reactions to other drugs, including beta-lactam antibiotics.
认识到青霉素和头孢菌素上变应原决定簇的结构异质性，揭示了侧链基团的重要性及其在许多对β-内酰胺类药物过敏反应中的作用。虽然已知青霉素和头孢菌素之间会发生变应原交叉反应，但这种识别和交叉敏感性的确切分子基础很少得到研究和确定。
对苄青霉素和头孢噻吩出现高发生率的阳性IgE抗体反应这一意外发现，促使开展血清学和免疫化学研究，以确定来自β-内酰胺抗生素两个不同家族的这些药物抗体识别的化学基础。
采用吸附研究来确定识别苄青霉素和头孢噻吩的是否为单一群体的抗体。通过使用精心挑选的β-内酰胺类药物、类似物和其他一些结构相关化学品进行定量半抗原抑制研究，来调查IgE抗体识别的精细结构特征。
用青霉噻唑酸固相进行的吸附研究清楚地表明，单一群体的交叉反应性抗体可识别苄青霉素和头孢噻吩。定量抑制结果，尤其是使用苯乙酸和2-噻吩乙酸以及与头孢噻吩具有相同（2-噻吩基）甲基侧链的头孢噻啶和头孢西丁的结果，表明亚甲基是在苄青霉素和头孢噻吩上识别的变应原决定簇的焦点。除亚甲基外，识别还扩展到包括酰胺基团在内的相邻结构，并微弱地延伸至β-内酰胺环。
结果证实，小至亚甲基的结构特征可能具有变应原重要性。在本案例中，该基团仅构成苄青霉素和头孢噻吩上不同侧链的一部分，与向β-内酰胺环延伸的相邻结构一起，解释了乍一看似乎没有密切关系的结构之间出现的交叉反应性。这种细微、微小、共同的结构特征可能会被免疫识别，并与包括β-内酰胺抗生素在内的其他药物的过敏反应有关。
