Basophilenaktivierungstests in der Diagnostik von Arzneimittelreaktionen

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.

Section: The Use Of Basophil Flow Cytometry In Allergy Diagnosis: Stamentioning

confidence: 50%

Basophil Activation Test in Allergy: Time for an Update?

Chirumbolo

2012

“…β -Lactams [88,89,90,91,92,93,94,95,96]. In quoting only one [88] of the several validated studies on BAT in the diagnosis of β-lactam allergy and in pretending that CD63 BAT was only performed in patients with positive skin tests to β-lactams, Kleine-Tebbe et al[ 1] have presented an incomplete view of the literature.…”

Section: Clinical Indications Of Batmentioning

confidence: 99%

“…Many of these studies have been reviewed recently [8,9,10]. Herewith, tables 1, 2, 3, 4, 5, 6, 7summarize the results of validated clinical studies performed with various allergens such as inhalant allergens [25,26,27,28,29,30,31,32,33] (table 1), hymenoptera venoms [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56] (table 2), latex [57,58,59,60,61,62,63] (table 3), food [64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80] (table 4) and drugs [81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,…”

Section: Clinical Issues In the Diagnostic Use Of Batmentioning

confidence: 99%

Diagnostic Tests Based on Human Basophils: More Potentials and Perspectives than Pitfalls

Weck

Sánz

Gamboa

et al. 2008

172

178

For the diagnosis of allergy, cellular basophil activation tests (BAT), e.g. histamine or sulfidoleukotriene release tests, have long been introduced, but the expression of basophil activation markers such as CD63 and CD203c detected by flow cytometry has attracted more recent attention. A recent opinion paper in this Journal has stressed not only the potential but also the possible pitfalls of flow-cytometric BAT. We have applied clinical validation of various BAT in various ways for several years, and our experience shows that these new technologies have more potentials and perspectives than pitfalls. A comprehensive review of clinically validated studies on allergy to aeroallergens, insect venoms, latex, food allergens and drugs, e.g. myorelaxants, β-lactams, pyrazolones and non-steroidal anti-inflammatory drugs, as well as chronic urticaria shows clearly that even with different protocols, reproducible and meaningful results can be obtained. Although the available technologies may still be optimized and better standardized, there are no serious reasons to deprive allergic patients of clinically indicated BAT, which can be performed reliably by any laboratory with allergy and flow-cytometric capacity and expertise.

“…They also provide limited explanation of the suspected underlying pathomechanism. A positive BAT (cutoff 10% CD63+ basophils) was demonstrated in another study in 30% of patients (n = 20) with NSAID hypersensitivity [48]. However, as long as it remains unclear whether the BAT can be used in elucidating non-IgE-mediated reactions, further studies are needed to clarify their role in NSAID hypersensitivity.…”

Section: Bat For Diagnostic Purposesmentioning

confidence: 99%

Diagnostic Tests Based on Human Basophils: Potentials, Pitfalls and Perspectives

Kleine-Tebbe¹,

Erdmann

Knol

et al. 2006

173

164

Human basophils are important tools for studying immediate-type hypersensitivity reactions since they release a variety of mediators (e.g., histamine, leukotriene C₄, IL-4 and IL-13) following allergen triggering. Several diagnostic tools have been introduced that measure either leukotriene production or the upregulation of surface markers (CD63 and CD203c) from these cells after antigen stimulation. However, a broad variability in basophil activity exists between different basophil donors and different antigens within one donor. This manifests itself in terms of their reactivity (maximum secretory response), based on the intracellular signaling of the basophils studied, and in terms of their sensitivity. The latter is governed by the number of IgE receptors per basophil, the ratio of antigen-specific IgE to total IgE, and by the number of cell surface antigen-specific IgE molecules for half-maximal responses, termed ‘intrinsic sensitivity’. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests for diagnostic purposes, each allergen should be pre-evaluated separately in order to determine a suitable stimulation range. Additionally, anti-IgE or anti-FcΕRIα antibodies should serve as positive controls, bearing in mind that 10–20% of basophil donors are not responsive to IgE-mediated stimulation. Diagnostic studies using CD63 or CD203c in hymenoptera, food and drug allergy are critically discussed. Basophil-based tests are indicated for allergy testing in selected cases but should only be performed by experienced laboratories.