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      Basophil Activation Test: Old and New Applications in Allergy

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          Abstract

          Purpose of Review

          The basophil activation test (BAT) using flow cytometry has supplanted traditional methods of measuring basophil degranulation using histamine and other mediator release, and can be used for clinical applications as well as to explore the immune mechanisms of effector cell response to allergen. This review discusses the advancements made in clinical, diagnostic and laboratory research of allergy utilizing an ever-evolving BAT.

          Recent Findings

          Being an in vitro surrogate of the allergic reaction that happens in vivo in the sick patient, the BAT can be used to support the diagnosis of various allergic conditions, such as food, drug, respiratory and insect venom allergies, and the assessment of clinical response to allergen-specific immunotherapy and other immunomodulatory treatments. The BAT can also be used for research purposes to explore the mechanisms of allergy and tolerance at the level of the basophil, for instance by manipulating IgE and IgG and their receptors and by studying intracellular signalling cascade in response to allergen.

          Summary

          This review covers the applications of the BAT to the clinical management of allergic patients and the increased understanding of the mechanisms of immune response to allergens as well as technological advancements made in recent years.

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

          H Hoffmann, A. F. G. N Santos, C Mayorga … (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.
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            Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children

            Alexandra F Santos, Abdel Douiri, Natalia Becares … (2014)
            Background Most of the peanut-sensitized children do not have clinical peanut allergy. In equivocal cases, oral food challenges (OFCs) are required. However, OFCs are laborious and not without risk; thus, a test that could accurately diagnose peanut allergy and reduce the need for OFCs is desirable. Objective To assess the performance of basophil activation test (BAT) as a diagnostic marker for peanut allergy. Methods Peanut-allergic (n = 43), peanut-sensitized but tolerant (n = 36) and non–peanut-sensitized nonallergic (n = 25) children underwent skin prick test (SPT) and specific IgE (sIgE) to peanut and its components. BAT was performed using flow cytometry, and its diagnostic performance was evaluated in relation to allergy versus tolerance to peanut and validated in an independent population (n = 65). Results BAT in peanut-allergic children showed a peanut dose-dependent upregulation of CD63 and CD203c while there was no significant response to peanut in peanut-sensitized but tolerant (P < .001) and non–peanut-sensitized nonallergic children (P < .001). BAT optimal diagnostic cutoffs showed 97% accuracy, 95% positive predictive value, and 98% negative predictive value. BAT allowed reducing the number of required OFCs by two-thirds. BAT proved particularly useful in cases in which specialists could not accurately diagnose peanut allergy with SPT and sIgE to peanut and to Arah2. Using a 2-step diagnostic approach in which BAT was performed only after equivocal SPT or Arah2-sIgE, BAT had a major effect (97% reduction) on the number of OFCs required. Conclusions BAT proved to be superior to other diagnostic tests in discriminating between peanut allergy and tolerance, particularly in difficult cases, and reduced the need for OFCs.
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              Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy.

              H Ipsen, C Ljørring, P Würtzen … (2012)
              Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated. A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation. © 2011 John Wiley & Sons A/S.
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                Author and article information

                Contributors
                Alexandra F. Santos: +44 (0) 20 7188 6424 , alexandra.santos@kcl.ac.uk
                Journal
                Journal ID (nlm-ta): Curr Allergy Asthma Rep
                Journal ID (iso-abbrev): Curr Allergy Asthma Rep
                Title: Current Allergy and Asthma Reports
                Publisher: Springer US (New York )
                ISSN (Print): 1529-7322
                ISSN (Electronic): 1534-6315
                Publication date (Electronic): 15 November 2018
                Publication date PMC-release: 15 November 2018
                Publication date (Print): 2018
                Volume: 18
                Issue: 12
                Electronic Location Identifier: 77
                Affiliations
                [1 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Women and Children’s Health (Paediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, , King’s College London, ; London, UK
                [2 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, , King’s College London, ; London, UK
                [3 ]ISNI 0000000122478951, GRID grid.14105.31, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, ; London, UK
                [4 ]GRID grid.425213.3, Children’s Allergies Department, Guy’s and St. Thomas’ NHS Foundation Trust, , St. Thomas’ Hospital, ; Westminster Bridge Road, London, UK
                Article
                Publisher ID: 831
                DOI: 10.1007/s11882-018-0831-5
                PMC ID: 6244909
                PubMed ID: 30430289
                SO-VID: 0cad0398-b2f2-4754-a448-5973a519646a
                Copyright © © The Author(s) 2018
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: King's College London
                Categories
                Subject: Immunologic/Diagnostic Tests in Allergy (P Matricardi, Section Editor)
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media, LLC, part of Springer Nature 2018

                ScienceOpen disciplines: Immunology
                Keywords: basophil activation test,diagnosis,ige,igg,allergy,immunotherapy
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: basophil activation test, diagnosis, ige, igg, allergy, immunotherapy

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