Drug Hypersensitivity (original) (raw)

The basophil activation test in immediate drug allergy

Acta clinica Belgica

Diagnosis of drug allergy is not always straight forward for several reasons. First, a broad spectrum of drugs can elicit various immune-mediated diseases with distinct pathomechanism, secondly, although exact epitope identification is not mandatory for clinical diagnosis, the epitope that causes the reaction is frequently unknown, thirdly in vitro or in vivo test results might not be predictive of a clinical situation, and finally the gold standard or reference test for diagnosis, the drug challenge, is a complicated and sometimes dangerous endeavour. Upon challenge with specific allergens that cross-link membrane-bound IgE antibodies, basophils upregulate the expression of different activation markers such as CD63 and CD203c. These immunophenotypic alterations can be detected on a single-cell basis by multicolour flow cytometry using specific monoclonal antibodies in the basophil activation test (BAT). This review intends to summarise our current experience with the BAT in the dia...

Recent applications of basophil activation tests in the diagnosis of drug hypersensitivity

Asia Pacific allergy, 2013

Immediate-type drug hypersensitivity is an increasingly significant clinical issue; however, the diagnosis is frequently hindered due to lack of safe and precise diagnostic tests. Flow cytometry-assisted basophil activation test is a safe in vitro diagnostic tool for assessing basophil activation upon allergen stimulation. In this review, we have summarized current literature on the diagnostic utilities, new indications, and methodological aspects of the basophil activation test for the diagnosis of drug hypersensitivity.

The basophil activation test in the diagnosis of immediate drug hypersensitivity

Expert Review of Clinical Immunology, 2011

Hypersensitivity reactions to drugs account for 15% of all adverse drug reactions and represent an important health problem with significant morbidity and mortality. This article describes the current applications and perspectives of the basophil activation test by flow cytometry in the diagnosis of immediate-type drug allergy, with particular focus on its diagnostic performance in allergy to neuromuscular blocking agents, antibiotics and NSAIDs and on future applications.

In vitro Tests: Basophil Activation Tests

Drug Hypersensitivity, 2007

In recent years, the quantification of basophil activation by flow cytometry (basophil activation test, BAT) has proven to be a useful tool for the assessment of immediate-type responses to allergens mediated by IgE or other mechanisms in drug-allergic patients. To date, most BAT studies reported in the literature have used CD69 or CD203c as markers to quantify basophil activation after antigen-specific stimulation. Technical variations, such as the use of whole blood or isolated leukocytes, the addition of IL-3, the conditions of storage of the blood sample, the time of incubation with allergens and their concentration, can affect the results of the BATs. The BAT is more sensitive and specific than other in vitro diagnostic techniques in drug allergy. In various studies, its sensitivity in allergy to musclerelaxant drugs ranges between 36 and 97.7%, with a specificity of around 95%. For ␤-lactam antibiotics, BAT sensitivity is 50% and its specificity 90%. For NSAIDs, sensitivity varies between 66 and 75%; specificity is about 93%. BAT is also a useful technique in the diagnosis of isolated cases of hypersensitivity to various other drugs and substances used in some therapeutic and diagnostic procedures.

Basophil Activation Test in Allergy: Time for an Update

International Archives of Allergy and Immunology, 2012

A wide range of reported evidence in the literature has shown that the quantification of basophil activation by flow cytometry (basophil activation test, BAT) has proven to be a useful tool for the assessment of immediate-type responses to allergens mediated by IgE or other mechanisms in allergic patients. The usefulness of BAT in anaphylactic adverse reactions, late-onset allergy and immunotherapy follow-up has also been demonstrated. To date, most BAT studies reported in the literature involved the capture of basophils only with a fluorochrome-labeled anti-IgE antibody and application of CD63 upregulation in order to evaluate the basophil response to allergens. Many issues need to be addressed, such as optimizing the analytical performance of the test, checking preanalytical conditions, the selection of the flow cytometry best gating protocol, the introduction of new algorithms and parameters, the search for new activation markers and the introduction of anti-IgE controls. BAT is certainly a useful technique, also for isolated cases of hypersensitivity to various other compounds and drugs, and an update of its application is certainly an interesting topic to expand the debate on allergy diagnosis.

In vitro diagnosis of immediate allergic reactions to drugs: an update

Journal of investigational allergology & clinical immunology, 2010

Evaluation of allergic reactions to drugs is difficult because of the poor sensitivity of in vivo tests, which makes controlled administration of the drug necessary to confirm the diagnosis. In vitro tests are important in order to avoid the risks of in vivo testing. In the present review, we describe the different methods for detecting immunoglobulin (Ig) E antibodies that are specific to drugs involved in the development of type I (immediate) reactions. The 2 main in vitro methods are immunoassays and the basophil activation test, both of which have sufficient sensitivity and specificity for the detection of specific IgE antibodies, although with a limited number of drugs, and they have proven complementary to in vivo methods. We show the importance of the allergological workup of the patient within less than 1 year from the occurrence of the allergic reaction in order to obtain positive results in both in vivo and in vitro tests.

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease

Allergy, 2015

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases. Introduction: The biological framework of BAT Basophils and mast cells are key effector cells in immediatetype allergic reactions, and the clinical impact of basophil activation test (BAT) is due to the unique ability of these cells to degranulate upon cross-linking of the specific IgE (sIgE) bound on membrane-bound high-affinity IgE receptor (FceRI) by allergen exposure. Basophils are estimated to have a half-life of less than a week (1), whereas mast cells persist for months in tissue (2). The density of FceRI-IgE

In vitro Diagnosis of Immediate Drug Hypersensitivity: Should We Go with the Flow?

International Archives of Allergy and Immunology, 2015

Background: Diagnosis of immediate drug hypersensitivity reactions (IDHRs) is based upon history taking, skin prick or intradermal tests and quantification of specific immunoglobulin E (IgE) antibodies. Unfortunately, this is often insufficient to correctly identify patients with IgE-mediated IDHRs and is impossible in the case of non-IgE-mediated IDHRs. Drug provocation tests (DPT) are considered the ‘gold standard' diagnostic but are not always possible, for ethical and practical reasons. Therefore, the validation of new cellular tests such as basophil activation testing (BAT) was necessary. This review focuses on the applications of BAT in IDHRs. Methods: A literature search was conducted, using the words basophil, flow cytometry, immediate drug allergy and drugs; this was complemented by the authors' own expertise. Results: BAT/HistaFlow® is a useful diagnostic tool in IDHRs, mainly used to diagnose allergy to neuromuscular blocking agents (NMBAs), antibiotics, nonsteroi...

In vitro allergy diagnosis: should we follow the flow?

Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004

During the last 5 years, an increasing number of studies have demonstrated that flow cytometric quantification of in vitro basophil activation can be a quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. So far, most assays have used CD63 as a basophil activation marker and native allergen extracts for stimulation. However, other basophil markers and recombinant allergens have recently been introduced. The technique has been applied for the diagnosis of allergy to pollen, house dust mite, food, natural rubber latex, hymenoptera venom and drugs. In addition, the technique has proven to be useful in non-IgE-mediated reactions such as hypersensitivity to drugs as well as detection of auto-antibodies in chronic urticaria. This review will focus on some specific issues: (1) principles of flow cytometric analysis of in vitro-activated basophils, (2) general technical aspects of the technique (including passive sensitization), (3) clinical applications and (4) recommendations for further development and evaluation of the technique.