Liu X-D, Gao N, Qiao H-L
Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.
Int J Clin Pharmacol Ther. 2011 Mar;49(3):206-16. doi: 10.5414/cpp49206.
Bata-lactam antibiotics are the most commonly used antibiotics which usually cause serious IgE-mediated allergic reactions. Of all bata-lactam antibiotics, penicillins have so far been the best-studied, but the studies of cephalosporins and their cross-reactivity with penicillins are rare. We sought to evaluate the IgE response in vitro and estimate cross-reactivity between penicillins and cephalosporins in patients allergic to penicillins.
We studied 87 control subjects and 420 subjects allergic to penicillins. Radioallergosorbent test (RAST) was performed to detect eight types of specific-penicillin IgE and eleven types of specific-cephalosporin IgE. The cross-reactivity and different molecules recognition by IgE were studied with a radioallergosorbent inhibition test.
Of 420 patients allergic to penicillins, 95 patients (22.62%) showed specific-cephalosporin IgE positive, 73 patients (17.38%) showed IgEs positive to both penicillins and cephalosporins. In specific-penicillin IgE positive group, the positive rate of specific-cephalosporin IgE was significantly higher than in specific-penicillin IgE negative group (27.14% vs. 14.57%, p < 0.01). In urticaria group, the positive rate of specific-cephalosporin IgE was significantly higher than in other symptoms group (30.65% vs. 8.11%, p < 0.05). The analysis of drugs which have the same or similar side-chains showed that benzylpenicillanyl-IgE (BPA-IgE), ampicillanyl-IgE (APA-IgE), amoxicillanyl-IgE (AXA-IgE) were respectively related to cephalothanyl-IgE (CLA-IgE), cephalexanyl-IgE (CEXA-IgE), cephalexanyl-IgE (CEXA-IgE)in sera of penicillin-allergic patients we studied, and compared with patients who had negative amoxicillin-IgE, the positive rates of specific-ampicillin IgE and specific-cephalexin IgE were significantly higher in patients who had positive amoxicillin-IgE (14.43% vs. 3.72%, 14.00% vs. 2.96%, p < 0.01). Radioallergosorbent test and radioallergosorbent inhibition test confirmed that both nuclear structure and R1 side-chain contribute to IgE recognition.
There exists cross-reactivity between cephalosporins and penicillins; patients allergic to several penicillins are more likely to develop allergic reaction to cephalosporins; due to sensitization to the similar structural characteristics (nuclear and R1 side-chain), penicillin-allergic patients may develop cross-allergic reactions with not only first-generation but also third-generation cephalosporins.
β-内酰胺类抗生素是最常用的抗生素，通常会引起严重的免疫球蛋白E（IgE）介导的过敏反应。在所有β-内酰胺类抗生素中，青霉素是目前研究最多的，但关于头孢菌素及其与青霉素交叉反应性的研究却很少。我们试图评估对青霉素过敏患者的体外IgE反应，并估计青霉素与头孢菌素之间的交叉反应性。
我们研究了87名对照受试者和420名对青霉素过敏的受试者。进行放射性变应原吸附试验（RAST）以检测8种特异性青霉素IgE和11种特异性头孢菌素IgE。通过放射性变应原吸附抑制试验研究IgE的交叉反应性和对不同分子的识别。
在420名对青霉素过敏的患者中，95名患者（22.62%）特异性头孢菌素IgE呈阳性，73名患者（17.38%）对青霉素和头孢菌素的IgE均呈阳性。在特异性青霉素IgE阳性组中，特异性头孢菌素IgE的阳性率显著高于特异性青霉素IgE阴性组（27.14%对14.57%，p<0.01）。在荨麻疹组中，特异性头孢菌素IgE的阳性率显著高于其他症状组（30.65%对8.11%，p<0.05）。对具有相同或相似侧链的药物分析表明，在我们研究的青霉素过敏患者血清中，苄青霉素基-IgE（BPA-IgE）、氨苄青霉素基-IgE（APA-IgE）、阿莫西林基-IgE（AXA-IgE）分别与头孢噻吩基-IgE（CLA-IgE）、头孢氨苄基-IgE（CEXA-IgE）、头孢氨苄基-IgE（CEXA-IgE）相关，与阿莫西林IgE阴性的患者相比，阿莫西林IgE阳性的患者中特异性氨苄青霉素IgE和特异性头孢氨苄IgE的阳性率显著更高（14.43%对3.72%，14.00%对2.96%，p<0.01）。放射性变应原吸附试验和放射性变应原吸附抑制试验证实，核结构和R1侧链均有助于IgE识别。
头孢菌素与青霉素之间存在交叉反应性；对几种青霉素过敏的患者更有可能对头孢菌素产生过敏反应；由于对相似结构特征（核和R1侧链）致敏，青霉素过敏患者不仅可能与第一代头孢菌素，还可能与第三代头孢菌素发生交叉过敏反应。
