Investigation of a BAT for improving diagnosis of drug allergy
Research type
Research Study
Full title
Investigation of the FlowCAST Basophil Activation Test for aiding diagnosis of penicillin and NMBA-induced allergy in a cohort of patients at Cambridge University Hospitals (CUH).
IRAS ID
313555
Contact name
Padmalal Gurugama
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust
Duration of Study in the UK
0 years, 8 months, 28 days
Research summary
Summary of Research
Allergies to drugs can be hard to diagnose as doctors rely on a combination of medical history, skin prick testing (pricking the skin with a tiny amount of the drug to see if it causes a reaction), and occasionally testing blood samples for drug-specific antibodies. Each of these tests have flaws and do not always indicate a full allergic response, so alternative tests are currently being researched to help make diagnosis clearer such as the basophil activation test (BAT).Basophils are immune cells that are found in the blood that help kickstart allergic reactions; if someone is allergic to a particular drug, they will have antibodies against that drug covering the surface of the basophils - these are called sensitised basophils. Once these sensitised basophils see the drug, they become “activated” and release potent compounds into the bloodstream that cause the symptoms associated with allergic reactions. The BAT uses blood samples from patients with drug allergies and exposes the basophils to the suspected drug in a test tube before looking at how many activated basophils are present. The activation of the basophils can be found by measuring if a molecule called CD63 is present on the surface of the cell, as this is shown to be increased on activated basophils but rarely on “normal” non-reactive basophils.
We expect a strong link between how allergic a patient is and how many activated basophils are present in their blood after exposure to the drug. We will be using samples from people with known allergies to penicillin to make sure that the BAT can predict an allergic response before testing how good it is with other drugs called neuromuscular blocking agents (NMBA), which are drugs used in surgery that are more difficult to diagnose allergies for than penicillin.
Summary of Results
Our objective was to determine the reliability of the basophil activation test (BAT) in giving accurate results compared with skin testing (the currently used method) in patients diagnosed with a drug allergy to one or more neuromuscular blocking agents (NMBA). We also wanted to compare the accuracy of antibody testing against the results of skin testing and the BAT in the same group of patients and healthy controls.
We included 11 patients diagnosed with NMBA allergy and 13 healthy volunteers with no known drug allergies in our study. All participants had blood samples taken which were tested for antibodies against the drugs Rocuronium and Suxamethonium. Nearly all participants also had a BAT performed on their blood samples to test their response to the drugs they were diagnosed as being allergic to. One healthy volunteer gave an unexpected strong positive result on BAT testing suggestive of drug allergy and was excluded from analysis. Two participants (1 patient and 1 healthy control) were unable to produce a valid BAT result and thus were excluded from analysis of BAT results.
The BAT correctly identified 4 out of 9 patients with a valid result who were diagnosed with NMBA allergy. No positive BAT results were seen for any patients who had previously tested negative on skin tests or who had ambiguous skin test results. Patients with positive skin tests were more likely to give a positive BAT result, with 4 out of 5 patients testing positive on both. Furthermore, positive BAT results were also unexpectedly seen in healthy controls. We concluded that in this population the BAT does not offer any additional information that could help diagnosing patients with allergy. There is also a risk of falsely giving positive results in otherwise healthy people.
Testing for Rocuronium IgE antibodies gave positive results in 4 out of 5 patients diagnosed with rocuronium allergy. All healthy controls and patients with other drug allergies tested negative for Rocuronium IgE antibodies. This test is currently not available outside of research use, however we concluded it would be a useful tool in diagnosis of people with suspected rocuronium allergy.REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
22/EM/0150
Date of REC Opinion
28 Jun 2022
REC opinion
Favourable Opinion