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Update on the Performance and Application of Basophil Activation Tests

  • IMMUNOLOGIC/DIAGNOSTIC TESTS IN ALLERGY (JL SCHMITZ, SECTION EDITOR)
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Abstract

The basophil activation test (BAT) is a flow-cytometry-based functional assay that assesses the degree of cell activation after exposure to a stimuli. Though no standardized technique currently exists, recent advances have improved the performance of this assay, including identification of new basophil-specific markers and comparisons of the expression of CD63 to CD203c during activation. The basophil activation test has also been validated for many IgE-mediated disease conditions, which have been extensively reviewed elsewhere. This review focuses on the most recent applications of this test to the diagnosis of allergy to drugs, foods, venoms, and pollens, and the evolving role of the BAT in monitoring immunotherapy.

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References

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  1. Lichtenstein LM, Norman PS, Winkenwerder WL. Clinical and in vitro studies on the role of immunotherapy in ragweed hay fever. Am J Med. 1968;44(4):514–24.

    Article  PubMed  CAS  Google Scholar 

  2. May CD. High spontaneous release of histamine in vitro from leukocytes of persons hypersensitive to food. J Allergy Clin Immunol. 1976;58(3):432–7.

    Article  PubMed  CAS  Google Scholar 

  3. Togias AG, Naclerio RM, Warner J, et al. Demonstration of inhibition of mediator release from human mast cells by azatadine base. in vivo and in vitro evaluation. JAMA. 1986;255(2):225–9.

    Article  PubMed  CAS  Google Scholar 

  4. Knol EF, Mul FP, Jansen H, Calafat J, Roos D. Monitoring human basophil activation via CD63 monoclonal antibody 435. J Allergy Clin Immunol. 1991;88(3 Pt 1):328–38.

    Article  PubMed  CAS  Google Scholar 

  5. Schroeder JT. Basophils: emerging roles in the pathogenesis of allergic disease. Immunol Rev. 2011;242(1):144–60.

    Article  PubMed  CAS  Google Scholar 

  6. Dvorak AM, Galli SJ, Schulman ES, Lichtenstein LM, Dvorak HF. Basophil and mast cell degranulation: ultrastructural analysis of mechanisms of mediator release. Fed Proc. 1983;42(8):2510–5.

    PubMed  CAS  Google Scholar 

  7. Dvorak AM, MacGlashan Jr DW, Morgan ES, Lichtenstein LM. Vesicular transport of histamine in stimulated human basophils. Blood. 1996;88(11):4090–101.

    PubMed  CAS  Google Scholar 

  8. Furuno T, Teshima R, Kitani S, Sawada J, Nakanishi M. Surface expression of CD63 antigen (AD1 antigen) in P815 mastocytoma cells by transfected IgE receptors. Biochem Biophys Res Commun. 1996;219(3):740–4.

    Article  PubMed  CAS  Google Scholar 

  9. MacGlashan Jr D. Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes. Clin Exp Allergy. 2010;40(9):1365–77.

    Article  PubMed  CAS  Google Scholar 

  10. Buhring HJ, Simmons PJ, Pudney M, et al. The monoclonal antibody 97A6 defines a novel surface antigen expressed on human basophils and their multipotent and unipotent progenitors. Blood. 1999;94(7):2343–56.

    PubMed  CAS  Google Scholar 

  11. Buhring HJ, Seiffert M, Giesert C, et al. The basophil activation marker defined by antibody 97A6 is identical to the ectonucleotide pyrophosphatase/phosphodiesterase 3. Blood. 2001;97(10):3303–5.

    Article  PubMed  CAS  Google Scholar 

  12. Hauswirth AW, Sonneck K, Florian S, et al. Interleukin-3 promotes the expression of E-NPP3/CD203C on human blood basophils in healthy subjects and in patients with birch pollen allergy. Int J Immunopathol Pharmacol. 2007;20(2):267–78.

    PubMed  CAS  Google Scholar 

  13. Monneret G, Boumiza R, Gravel S, et al. Effects of prostaglandin D(2) and 5-lipoxygenase products on the expression of CD203c and CD11b by basophils. J Pharmacol Exp Ther. 2005;312(2):627–34.

    Article  PubMed  CAS  Google Scholar 

  14. Macglashan Jr D. Marked differences in the signaling requirements for expression of CD203c and CD11b versus CD63 expression and histamine release in human basophils. Int Arch Allergy Immunol. 2012;159(3):243–52.

    Article  PubMed  CAS  Google Scholar 

  15. Hennersdorf F, Florian S, Jakob A, et al. Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-dependent upregulation. Cell Res. 2005;15(5):325–35.

    Article  PubMed  CAS  Google Scholar 

  16. Ebo DG, Dombrecht EJ, Bridts CH, Aerts NE, de Clerck LS, Stevens WJ. Combined analysis of intracellular signalling and immunophenotype of human peripheral blood basophils by flow cytometry: a proof of concept. Clin Exp Allergy. 2007;37(11):1668–75.

    Article  PubMed  CAS  Google Scholar 

  17. Wolanczyk-Medrala A, Barg W, Liebhart J, et al. Validation of basophil CD164 upregulation for pollen allergy diagnosis. Arch Immunol Ther Exp (Warsz). 2010;58(6):459–65.

    Article  CAS  Google Scholar 

  18. Sturm GJ, Kranzelbinder B, Sturm EM, Heinemann A, Groselj-Strele A, Aberer W. The basophil activation test in the diagnosis of allergy: technical issues and critical factors. Allergy. 2009;64(9):1319–26.

    Article  PubMed  CAS  Google Scholar 

  19. • Sturm EM, Kranzelbinder B, Heinemann A, Groselj-Strele A, Aberer W, Sturm GJ. CD203c-based basophil activation test in allergy diagnosis: characteristics and differences to CD63 upregulation. Cytometry B Clin Cytom. 2010;78(5):308–18. This article similarly examined the effect of technical issues on the expression of CD203c.

    PubMed  Google Scholar 

  20. Sousa N, Martinez-Aranguren R, Fernandez-Benitez M, Ribeiro F, Sanz ML. Comparison of basophil activation test results in blood preserved in acid citrate dextrose and EDTA. J Investig Allergol Clin Immunol. 2010;20(6):535–6.

    PubMed  CAS  Google Scholar 

  21. Hausmann OV, Gentinetta T, Fux M, Ducrest S, Pichler WJ, Dahinden CA. Robust expression of CCR3 as a single basophil selection marker in flow cytometry. Allergy. 2011;66(1):85–91.

    Article  PubMed  CAS  Google Scholar 

  22. Abuaf N, Rostane H, Rajoely B, et al. Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy. Clin Exp Allergy. 2008;38(6):921–8.

    Article  PubMed  CAS  Google Scholar 

  23. Eberlein B, Leon Suarez I, Darsow U, Rueff F, Behrendt H, Ring J. A new basophil activation test using CD63 and CCR3 in allergy to antibiotics. Clin Exp Allergy. 2010;40(3):411–8.

    Article  PubMed  CAS  Google Scholar 

  24. Monneret G. CCR3 for basophil activation test: a necessary but insufficient step. Clin Exp Allergy. 2010;40(6):953. author reply 954.

    Article  PubMed  CAS  Google Scholar 

  25. Monneret G. Is this time for CRTH2/DP2 in a flow cytometric basophil activation test? Clin Exp Allergy. 2008;38(7):1239–40.

    Article  PubMed  CAS  Google Scholar 

  26. Boumiza R, Debard AL, Monneret G. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives. Clin Mol Allergy. 2005;3:9.

    Article  PubMed  Google Scholar 

  27. Abuaf N, Rostane H, Barbara J, et al. Comparison of CD63 upregulation induced by NSAIDs on basophils and monocytes in patients with NSAID hypersensitivity. J Allergy (Cairo) 2012;2012:580873.

  28. Wolanczyk-Medrala A, Gogolewski G, Liebhart J, et al. A new variant of the basophil activation test for allergen-induced basophil CD63 upregulation. The effect of cetirizine. J Investig Allergol Clin Immunol. 2009;19(6):465–73.

    PubMed  CAS  Google Scholar 

  29. Mastalerz L, Setkowicz M, Sanak M, Szczeklik A. Hypersensitivity to aspirin: common eicosanoid alterations in urticaria and asthma. J Allergy Clin Immunol. 2004;113(4):771–5.

    Article  PubMed  CAS  Google Scholar 

  30. Korosec P, Mavsar N, Bajrovic N, Silar M, Mrhar A, Kosnik M. Basophil responsiveness and clinical picture of acetylsalicylic acid intolerance. Int Arch Allergy Immunol. 2011;155(3):257–62.

    Article  PubMed  CAS  Google Scholar 

  31. Gomez E, Blanca-Lopez N, Torres MJ, et al. Immunoglobulin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Clin Exp Allergy. 2009;39(8):1217–24.

    Article  PubMed  CAS  Google Scholar 

  32. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the japanese committee on the safety of contrast media. Radiology. 1990;175(3):621–8.

    PubMed  CAS  Google Scholar 

  33. Wolf GL, Arenson RL, Cross AP. A prospective trial of ionic vs nonionic contrast agents in routine clinical practice: comparison of adverse effects. AJR Am J Roentgenol. 1989;152(5):939–44.

    PubMed  CAS  Google Scholar 

  34. Brockow K, Romano A, Aberer W, et al. Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a european multicenter study. Allergy. 2009;64(2):234–41.

    Article  PubMed  CAS  Google Scholar 

  35. Javaloyes G, Goikoetxea MJ, Sanz ML, Cabrera-Freitag P, Gastaminza G. Basophil activation test in the diagnosis of gadobutrol anaphylaxis. Ann Allergy Asthma Immunol. 2012;108(4):286–7.

    Article  PubMed  Google Scholar 

  36. Pinnobphun P, Buranapraditkun S, Kampitak T, Hirankarn N, Klaewsongkram J. The diagnostic value of basophil activation test in patients with an immediate hypersensitivity reaction to radiocontrast media. Ann Allergy Asthma Immunol. 2011;106(5):387–93.

    Article  PubMed  Google Scholar 

  37. Ben Said B, Berard F, Bienvenu J, Nicolas JF, Rozieres A. Usefulness of basophil activation tests for the diagnosis of IgE-mediated allergy to quinolones. Allergy. 2010;65(4):535–6.

    Article  PubMed  CAS  Google Scholar 

  38. Aranda A, Mayorga C, Ariza A, et al. In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy. 2011;66(2):247–54.

    Article  PubMed  CAS  Google Scholar 

  39. Rouzaire P, Nosbaum A, Denis L, et al. Negativity of the basophil activation test in quinolone hypersensitivity: a breakthrough for provocation test decision-making. Int Arch Allergy Immunol. 2012;157(3):299–302.

    Article  PubMed  Google Scholar 

  40. Cabrera-Freitag P, Gastaminza G, Goikoetxea MJ, Lafuente A, de la Borbolla JM, Sanz ML. Immediate allergic reaction to atropine in ophthalmic solution confirmed by basophil activation test. Allergy. 2009;64(9):1388–9.

    Article  PubMed  CAS  Google Scholar 

  41. Soriano Gomis V, Perez Sempere A, Gonzalez Delgado P, Sempere JM, Niveiro Hernandez E, Marco FM. Glatiramer acetate anaphylaxis: detection of antibodies and basophil activation test. J Investig Allergol Clin Immunol. 2012;22(1):65–6.

    PubMed  CAS  Google Scholar 

  42. Ben Said B, Leray V, Nicolas JF, Rozieres A, Berard F. Methylprednisolone-induced anaphylaxis: diagnosis by skin test and basophil activation test. Allergy. 2010;65(4):531–2.

    Article  PubMed  CAS  Google Scholar 

  43. Bobadilla-Gonzalez P, Perez-Rangel I, Camara-Hijon C, Garcia-Menaya JM, Sanchez-Vega S. Positive basophil activation test result in a patient with acute urticaria induced by cetirizine and desloratadine. Ann Allergy Asthma Immunol. 2011;106(3):258–9.

    Article  PubMed  Google Scholar 

  44. Matsuo H, Dahlstrom J, Tanaka A, et al. Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis. Allergy. 2008;63(2):233–6.

    Article  PubMed  CAS  Google Scholar 

  45. Fukutomi Y, Itagaki Y, Taniguchi M, et al. Rhinoconjunctival sensitization to hydrolyzed wheat protein in facial soap can induce wheat-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol. 2011;127(2):531–3. e1-3.

    Article  PubMed  CAS  Google Scholar 

  46. Chinuki Y, Kaneko S, Dekio I, et al. CD203c expression-based basophil activation test for diagnosis of wheat-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol. 2012;129(5):1404–6.

    Article  PubMed  CAS  Google Scholar 

  47. Rubio A, Vivinus-Nebot M, Bourrier T, Saggio B, Albertini M, Bernard A. Benefit of the basophil activation test in deciding when to reintroduce cow's milk in allergic children. Allergy. 2011;66(1):92–100.

    Article  PubMed  CAS  Google Scholar 

  48. Ford LS, Bloom KA, Nowak-Wegrzyn AH, Shreffler WG, Masilamani M, Sampson HA. Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow's milk tolerance. J Allergy Clin Immunol. 2012.

  49. Ocmant A, Mulier S, Hanssens L, et al. Basophil activation tests for the diagnosis of food allergy in children. Clin Exp Allergy. 2009;39(8):1234–45.

    Article  PubMed  CAS  Google Scholar 

  50. Sabato V, van Hengel AJ, De Knop KJ, et al. Basophil activation reveals divergent patient-specific responses to thermally processed peanuts. J Investig Allergol Clin Immunol. 2011;21(7):527–31.

    PubMed  CAS  Google Scholar 

  51. Sabato V, van Hengel AJ, De Knop KJ, et al. Human basophils: a unique biological instrument to detect the allergenicity of food. J Investig Allergol Clin Immunol. 2011;21(3):179–84.

    PubMed  CAS  Google Scholar 

  52. Dolle S, Lehmann K, Schwarz D, et al. Allergenic activity of different tomato cultivars in tomato allergic subjects. Clin Exp Allergy. 2011;41(11):1643–52.

    Article  PubMed  CAS  Google Scholar 

  53. Raap U, Wieczorek D, Schenck F, Kapp A, Wedi B. The basophil activation test is a helpful diagnostic tool in anaphylaxis to sesame with false-negative specific IgE and negative skin test. Allergy. 2011;66(11):1497–9.

    Article  PubMed  CAS  Google Scholar 

  54. Lee JY, Jin HJ, Park JW, Jung SK, Jang JY, Park HS. A case of korean ginseng-induced anaphylaxis confirmed by open oral challenge and basophil activation test. Allergy Asthma Immunol Res. 2012;4(2):110–1.

    Article  PubMed  Google Scholar 

  55. Garcia-Ortega P, Scorza E, Teniente A. Basophil activation test in the diagnosis of sulphite-induced immediate urticaria. Clin Exp Allergy. 2010;40(4):688. author reply 689-90.

    Article  PubMed  CAS  Google Scholar 

  56. Kim JH, An S, Kim JE, Choi GS, Ye YM, Park HS. Beef-induced anaphylaxis confirmed by the basophil activation test. Allergy Asthma Immunol Res. 2010;2(3):206–8.

    Article  PubMed  Google Scholar 

  57. Hunt KJ, Valentine MD, Sobotka AK, Benton AW, Amodio FJ, Lichtenstein LM. A controlled trial of immunotherapy in insect hypersensitivity. N Engl J Med. 1978;299(4):157–61.

    Article  PubMed  CAS  Google Scholar 

  58. Ebo DG, Hagendorens MM, Bridts CH, De Clerck LS, Stevens WJ. Hymenoptera venom allergy: taking the sting out of difficult cases. J Investig Allergol Clin Immunol. 2007;17(6):357–60.

    PubMed  CAS  Google Scholar 

  59. Korosec P, Erzen R, Silar M, Bajrovic N, Kopac P, Kosnik M. Basophil responsiveness in patients with insect sting allergies and negative venom-specific immunoglobulin E and skin prick test results. Clin Exp Allergy. 2009;39(11):1730–7.

    Article  PubMed  CAS  Google Scholar 

  60. Bonadonna P, Zanotti R, Melioli G, et al. The role of basophil activation test in special populations with mastocytosis and reactions to hymenoptera sting. Allergy. 2012;67(7):962–5.

    Article  PubMed  CAS  Google Scholar 

  61. •• Mertens M, Amler S, Moerschbacher BM, Brehler R. Cross-reactive carbohydrate determinants strongly affect the results of the basophil activation test in hymenoptera-venom allergy. Clin Exp Allergy. 2010;40(9):1333–45. This paper used the basophil activation test to assess the biologic activity of cross-reactive carbohydrate determinants.

    Article  PubMed  CAS  Google Scholar 

  62. Eberlein B, Krischan L, Darsow U, Ollert M, Ring J. Double positivity to bee and wasp venom: improved diagnostic procedure by recombinant allergen-based IgE testing and basophil activation test including data about cross-reactive carbohydrate determinants. J Allergy Clin Immunol. 2012;130(1):155–61.

    Article  PubMed  CAS  Google Scholar 

  63. Khan FM, Ueno-Yamanouchi A, Serushago B, et al. Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific immunoglobulin-E. Allergy Asthma Clin Immunol. 2012;8(1):1.

    Article  PubMed  Google Scholar 

  64. Ozdemir SK, Guloglu D, Sin BA, Elhan AH, Ikinciogullari A, Misirligil Z. Reliability of basophil activation test using CD203c expression in diagnosis of pollen allergy. Am J Rhinol Allergy. 2011;25(6):e225–31.

    Article  PubMed  Google Scholar 

  65. •• Erzen R, Kosnik M, Silar M, Korosec P. Basophil response and the induction of a tolerance in venom immunotherapy: a long-term sting challenge study. Allergy. 2012;67(6):822–30. This paper monitored basophil response in 23 patients undergoing venom immunotherapy. They found that basophil activation was decreased one year after completion of immunotherapy.

    Article  PubMed  CAS  Google Scholar 

  66. Zitnik SE, Vesel T, Avcin T, Silar M, Kosnik M, Korosec P. Monitoring honeybee venom immunotherapy in children with the basophil activation test. Pediatr Allergy Immunol. 2012;23(2):166–72.

    Article  PubMed  Google Scholar 

  67. Cichocka-Jarosz E, Dorynska A, Pietrzyk JJ, Spiewak R. Laboratory markers of mast cell and basophil activation in monitoring rush immunotherapy in bee venom-allergic children. Immunotherapy. 2011;3(8):1013–7.

    Article  PubMed  CAS  Google Scholar 

  68. Van Overtvelt L, Baron-Bodo V, Horiot S, et al. Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy. Allergy. 2011;66(12):1530–7.

    Article  PubMed  Google Scholar 

  69. Lasa Luaces EM, Tabar Purroy AI, Garcia Figueroa BE, et al. Component-resolved immunologic modifications, efficacy, and tolerance of latex sublingual immunotherapy in children. Ann Allergy Asthma Immunol. 2012;108(5):367–72.

    Article  PubMed  CAS  Google Scholar 

  70. Swamy RS, Reshamwala N, Hunter T, et al. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol. 2012;130(1):215–24. e7.

    Article  PubMed  CAS  Google Scholar 

  71. Patil SP, Wang J, Song Y, et al. Clinical safety of food allergy herbal formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: extended phase I study. J Allergy Clin Immunol. 2011;128(6):1259–65. e2.

    Article  PubMed  Google Scholar 

  72. Kopac P, Rudin M, Gentinetta T, et al. Continuous apple consumption induces oral tolerance in birch-pollen-associated apple allergy. Allergy. 2012;67(2):280–5.

    Article  PubMed  CAS  Google Scholar 

  73. Bavbek S, Ikinciogullari A, Dursun AB, et al. Upregulation of CD63 or CD203c alone or in combination is not sensitive in the diagnosis of nonsteroidal anti-inflammatory drug intolerance. Int Arch Allergy Immunol. 2009;150(3):261–70.

    Article  PubMed  CAS  Google Scholar 

  74. De Week AL, Sanz ML, Gamboa PM, et al. Diagnosis of immediate-type beta-lactam allergy in vitro by flow-cytometric basophil activation test and sulfidoleukotriene production: a multicenter study. J Investig Allergol Clin Immunol. 2009;19(2):91–109.

    PubMed  Google Scholar 

  75. Kim MS, Cho YJ. Flow cytometry-assisted basophil activation test as a safe diagnostic tool for aspirin/NSAID hypersenstivity. Allergy Asthma Immunol Res. 2012;4(3):137–42.

    Article  PubMed  CAS  Google Scholar 

  76. Rodriguez-Trabado A, Camara-Hijon C, Ramos-Cantarino A, et al. Basophil activation test for the in vitro diagnosis of nonsteroidal anti-inflammatory drug hypersensitivity. Allergy Asthma Proc. 2008;29(3):241–9.

    Article  PubMed  CAS  Google Scholar 

  77. Peternelj A, Silar M, Bajrovic N, et al. Diagnostic value of the basophil activation test in evaluating hymenoptera venom sensitization. Wien Klin Wochenschr. 2009;121(9–10):344–8.

    Article  PubMed  Google Scholar 

  78. Frezzolini A, Cadoni S, De Pita O. Usefulness of the CD63 basophil activation test in detecting anisakis hypersensitivity in patients with chronic urticaria: diagnosis and follow-up. Clin Exp Dermatol. 2010;35(7):765–70.

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, 2B71B, Baltimore, MD, 21224, USA

    Emily C. McGowan & Sarbjit Saini

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McGowan, E.C., Saini, S. Update on the Performance and Application of Basophil Activation Tests. Curr Allergy Asthma Rep 13, 101–109 (2013). https://doi.org/10.1007/s11882-012-0324-x

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