Neis Mark M, Merk Hans F
Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.
Cutan Ocul Toxicol. 2012 Jun;31(2):117-23. doi: 10.3109/15569527.2011.621080. Epub 2011 Oct 13.
Stings by insects can precipitate many signs and symptoms of dermatological and ocular diseases. Of particular importance is the anaphylaxis after Hymenoptera stings. Selection of the appropriate venom for immunotherapy requires a precise diagnosis, which is frequently difficult to confirm since the history presented by the patient is many times not conclusive and diagnostic tests are often positive for bee venom (BV) and vespula venom (VV). This double positivity is either caused by true double sensitization or by antibodies cross-reactive to homologous peptide sequences or to cross-reactive carbohydrate determinants (CCDs). In this study, we analyzed in 39 patients, tested positive for specific immunoglobulin E (sIgE) against BV and VV and CCDs whether the routine detection of sIgE against the recombinant species-specific major allergens (SSMAs) rApi m1 and rVes v5 enables the discrimination between genuine double sensitization and cross reactivity and therefore may be superior to other in vitro assays such as IgE-inhibition test or the basophil activation test.
Thirty-nine patients each with allergic reactions to vespula and/or honey bee stings and tested positive for sIgE antibodies against CCDs were analyzed for sIgE against BV, VV, CCDs (MUFX3) and SSMAs by UNICAP (CAP) and to BV, VV, bromelain, horseradish peroxidase and ascorbat oxidase by Immulite 2000 (IMMU). In 12 cases results from a basophil activation test, in nine cases results from IgE-inhibition assays and in 10 cases an unambiguous history of the patient were taken into consideration.
A definite diagnosis could be assigned to each patient: sensitization to BV n = 7, sensitization to VV n = 29 and true double sensitization to both venoms n = 3. Detection of sIgE against BV and VV by CAP leads in three cases to the diagnosis BV allergy, in 35 cases to the diagnosis double sensitization and in one case to the diagnosis VV allergy. Detection of sIgE against BV and VV by IMMU leads in five cases to the diagnosis BV allergy, in 27 cases to the diagnosis double sensitization and in seven cases to the diagnosis VV allergy. Detection of sIgE against rApi m1 and rVes v5 by CAP leads in six cases to the diagnosis BV allergy, in eight cases to the diagnosis double sensitization, in 21 cases to the diagnosis VV allergy and in four cases to a false double-nagative result implicating no allergy.
Detection of sIgE to rApi m 1 and rVes v 5 by CAP is the most reliable diagnostic procedure to discriminate between true double sensitization and cross reactivity in patients with double-positive IgE results to venom extracts in the presence of sIgE against CCDs. In this study, however, we demonstrate that in nine of 39 patients tested positive for sIgE against CCDs, even the allergen component based diagnostic produces false double-positive and also false double-negative test results. Thus, we conclude that especially in hard to diagnose CCD positive patients beside the detection of sIgE, in vitro assays such as the IgE-inhibition test or the basophil activation test are still of importance. Detection of sIgE against only two SSMAs is not sufficient for a precise diagnosis. We propose inclusion of further SSMAs in diagnostic procedures.
昆虫叮咬可引发许多皮肤和眼部疾病的体征和症状。膜翅目昆虫叮咬后的过敏反应尤为重要。选择合适的毒液进行免疫治疗需要精确诊断，而这往往很难确定，因为患者提供的病史很多时候并不具有决定性，且诊断测试对蜂毒（BV）和黄蜂毒液（VV）常常呈阳性。这种双重阳性要么是由真正的双重致敏引起，要么是由与同源肽序列或交叉反应性碳水化合物决定簇（CCD）交叉反应的抗体引起。在本研究中，我们分析了39例针对BV、VV和CCD特异性免疫球蛋白E（sIgE）检测呈阳性的患者，检测针对重组物种特异性主要变应原（SSMA）rApi m1和rVes v5的sIgE是否能够区分真正的双重致敏和交叉反应，因此可能优于其他体外检测方法，如IgE抑制试验或嗜碱性粒细胞活化试验。
39例对黄蜂和/或蜜蜂叮咬有过敏反应且针对CCD的sIgE抗体检测呈阳性的患者，通过UNICAP（CAP）分析针对BV、VV、CCD（MUFX3）和SSMA的sIgE，通过Immulite 2000（IMMU）分析针对BV、VV、菠萝蛋白酶、辣根过氧化物酶和抗坏血酸氧化酶的sIgE。12例考虑了嗜碱性粒细胞活化试验结果，9例考虑了IgE抑制试验结果，10例考虑了患者明确的病史。
可为每位患者做出明确诊断：对BV致敏n = 7例，对VV致敏n = 29例，对两种毒液真正双重致敏n = 3例。通过CAP检测针对BV和VV的sIgE，3例诊断为BV过敏，35例诊断为双重致敏，1例诊断为VV过敏。通过IMMU检测针对BV和VV的sIgE，5例诊断为BV过敏，27例诊断为双重致敏，7例诊断为VV过敏。通过CAP检测针对rApi m1和rVes v5的sIgE，6例诊断为BV过敏，8例诊断为双重致敏，21例诊断为VV过敏，4例出现假双阴性结果提示无过敏。
在存在针对CCD的sIgE的情况下，对于毒液提取物IgE结果呈双阳性的患者，通过CAP检测针对rApi m1和rVes v5的sIgE是区分真正双重致敏和交叉反应的最可靠诊断方法。然而，在本研究中，我们证明在39例针对CCD的sIgE检测呈阳性的患者中，有9例即使基于变应原成分的诊断也会产生假双阳性和假双阴性检测结果。因此，我们得出结论，特别是在难以诊断的CCD阳性患者中，除了检测sIgE外，体外检测方法如IgE抑制试验或嗜碱性粒细胞活化试验仍然很重要。仅检测针对两种SSMA的sIgE不足以进行精确诊断。我们建议在诊断程序中纳入更多的SSMA。
