Is the BAT inhibition able to replace sting challenges?

Insect venom allergy is the major cause for severe allergic reactions in Europe. Wasps and honeybees are responsible for the majority of these allergic reactions and about 80% of venom allergic patients suffer from vespid venom allergy. Symptoms range from generalized skin symptoms (wheals, swellings) to respiratory or cardiovascular problems such as asthma, dizziness, loss of conscious ness, or cardiac arrest. The regular administration of insect venom (venom immunotherapy) over up to 5 years is a well-established therapy, providing long-term protection from further systemic sting reactions in the majority of patients. However, there is no laboratory test which is able to identify patients who will still react to an insect sting. The only reliable method available is stinging patients with living insects (sting challenges). The key issue is that only few centers in Europe perform s ting challenges and many patients have no access to these tests. Therefore, it is of utmost importance to find a method which is able to identify patients who are still at risk for future allergic sting reactions. The inhibition of the basophil activation test (BAT) could be a potential method to monitor the effectiveness of immunotherapy. Basophils are cells which are activated in acute allergic reactions. The basophil activation of blood donors with a bee or a vespid venom allergy can be measured after adding sera from allergic patients undergoing immunotherapy. In a preliminary study, we found that the activation of basophils could be inhibited in all patients treated with vespid venom immunotherapy but these results must be confirmed in a larger study. In this study, a total of 219 patients with vespid venom allergy will be included. Those patients who are receiving or who have already finished venom immunotherapy will be sting challenged and blood samples will be taken to perform BAT inhibition experiments. At the same time, donors with confirmed vespid venom allergy, who have not undergone immunotherapy, will be recruited for a blood donation, which is necessary for the BAT inhibition tests. If results of the preliminary study could be confirmed, the BAT inhibition will facilitate monitoring the effectiveness of vespid venom immunotherapy and patients would benefit from an early detec tion of lacking tolerance and consequently from the increased venom dose preventing future life threatening systemic sting reactions.

Allergy to bee and wasp venom is one of the most common causes of life-threatening allergic reactions in Europe. Fortunately, there is a highly effective treatment: venom immunotherapy. Patients receive injections of insect venom over several years, and in almost all cases, they are then protected from severe reactions. Until now, this protection can only be confirmed by a real sting under medical supervision, the so called sting challenge; a demanding procedure that is offered by only a few specialized centers. The aim of our project is to establish a blood test that can reliably show whether a person is protected from future systemic sting reactions or not. For this test, special allergy cells from the blood are mixed with the serum of treated patients. If the therapy has worked well, the serum contains protective factors that "switch off" these allergy cells. If the cells no longer react, this is a clear sign that the treatment was successful. First results from our large study are very promising. At the same time, we were able to significantly improve the therapy itself: a new up-dosing protocol, which is used at the beginning of the immunotherapy to increase venom doses, shortens the start of treatment from 15 to just 7 weeks - without any loss of effectiveness. This saves time and is gentler for patients. The new laboratory test also helps to clarify complex allergy cases, so that many people do not have to be treated unnecessarily with both, bee and wasp venom. Thanks to continued funding, the study is still ongoing. We are confident that soon there will be enough data to establish the blood test as a safe alternative to the sting challenge.