EDITORIAL Clinical & Experimental Allergy Basophil activation test in the diagnosis of insect venom allergies This editorial discusses the findings of the paper in this issue by Korosec et al. [20] pp. 1730–7. B. Eberlein 1,2 1 Division of Environmental Dermatology and Allergology, Helmholtz Center Munich for Environmental Health/TUM, Munich, Germany and 2 Department of Dermatology and Allergy Biederstein, Technische Universit ¨ at M ¨ unchen, Munich, Germany Life-threatening anaphylactic reactions to hymenoptera stings occur in 0.8–5% of the general population. Treat- ment of this IgE-mediated allergy with specific immu- notherapy is highly effective. About 80–100% of those who formerly displayed a systemic reaction no longer do so when re-stung following the initiation of treatment. The diagnosis of insect venom allergy and the indication for specific immunotherapy is based on patient history, skin testing and demonstration of hymenoptera venom- specific IgE antibodies. Stepwise incremental venom skin tests are recommended. The sensitivity of skin prick tests (SPT) is lower than that of intradermal tests. These in vivo and in vitro tests are performed to demonstrate IgE- mediated reactions. In many cases, the results of these tests form the basis of the indication for immunotherapy with the relevant insect [1]. Another method of identifying IgE-mediated reactions is the analysis of IgE-bearing basophils. In the 1970s the Lichtenstein group used basophil histamine release to characterize the allergenic components of insect venom and as a diagnostic method for a small number of patients [2]. Later, sensitivity and specificity for venom-induced histamine release was determined in a large group of insect venom-allergic patients [3]. Measurement of de novo synthesized sulphidoleukotrienes after allergen sti- mulation was introduced in 1993 by de Weck et al. [4] and used for the diagnosis of insect venom allergy. The concept of flow cytometric measurement of CD63 expres- sion as a marker of basophil activation was published in 1991 [5]. The CD63 marker is a 53 kDa glycoprotein present on the lysosome membrane and is expressed with a high density on activated basophil membrane. In patients with insect venom allergy, the basophil activation test (BAT) with hymenoptera venom achieved better results than histamine release and equal results to leukotriene C4 release [6]. The sensitivity of the test was 85–100%; specificity was 83–100% in several studies showing the reliability of the test for insect venom allergy [7–9]. CD203c (ectonucleotide pyrophosphatase/phospho- diesterase 3 as a type II transmembrane protein), is another basophil-specific activation marker not expressed on other blood lymphocytes. It is upregulated in response to IgE receptor cross-linking similar to CD63, but it has been shown that CD203c and CD63 upregulation appears to be regulated by different pathways and follows differ- ent kinetics [10]. For the BAT using CD203c, a sensitivity of between 89% and 100% and a specificity of between 89% and 92% was found in patients allergic to insect venom [11–13]. BATs can also help to solve several problems in the diagnosis of insect venom allergy. In cases with negative skin tests and negative RAST or contradictory results, several researchers have shown that BATs (if possible in combination with a cellular antigen stimulation test) are useful in demonstrating IgE-mediated reactivity [8, 14, 15]. Double positivity has also proved problematic: this means patients with allergic reactions to honey bee or Vespula stings also have specific IgE for the other venom, making it difficult to select which venom to use for immunotherapy. Double positivity in diagnostic tests may be caused by true double sensitization to both venoms, or by cross-reactions that occur either on a peptide basis or may be related to so called cross-reacting carbohydrate determinants. In some cases, BATs can support the decision to use immunotherapy with one insect [8, 9, 15]. Correspondence: Prof. Dr Bernadette Eberlein, Klinik und Poliklinik f¨ ur Dermatolo- gie und Allergologie am Biederstein, Technische Universit¨ at M¨ unchen, Biedersteiner Straße 29, D-80802 Munich, Germany. E-mail: eberlein@lrz.tum.de Cite this as: B. Eberlein, Clinical & Experimental Allergy , 2009 (39) 1633–1634. doi: 10.1111/j.1365-2222.2009.03375.x Clinical & Experimental Allergy, 39, 1633–1634  c 2009 Blackwell Publishing Ltd