Basophil activation test versus radio-immunoassay in the diagnosis of β-lactam immediate-type hypersensitivity reactions

Open access


Background and aims: to assess the sensitivity and specificity for the basophil activation test (BAT) and the detection of drug-specific antibodies (IgE) in the retrospective diagnosis of β-lactam allergy by using assay- specific thresholds as resulted from the performance of receiver operating characteristics curve (ROC) analysis and to describe a sequential algorithm that might increase diagnostic sensitivity and reduce the number of patients that should undergo drug challenge tests by the joint use of in vivo and in vitro diagnostic tests. Methods: 37 patients with suspected β-lactam immediate-type hypersensitivity reactions were tested for the culprit drug. 31 healthy controls were similarly tested. BAT was performed with Flow2Cast technique (Bühlmann Laboratories, Switzerland). Drug-specific IgE antibodies were detected using “sandwich”-type radio-immunoassay (RIA) with sepharose as solid phase (Pathologie Université „H. Poincare”, France). Results: ROC curve analysis identifies an optimal threshold>1.9 for RIA positivity, with 70.3% sensitivity and 90.3% specificity. For BAT, an optimal threshold>1.97 yields 51.4% sensitivity and 90.3% specificity. 89.18% of the patients were diagnosed by the combined use of skin tests and in vitro tests results, while 10.82% of the patients had negative tests results. Conclusions: RIA seems to have higher sensitivity than BAT (70.3% versus 51.4%) for β-lactams. The joint use of allergy diagnostic tests has 89.18% sensitivity. A combination of allergologic skin tests, detection of antibiotic- specific antibodies, followed by BAT may be suitable for investigating β-lactam hypersensitivity reactions since no diagnostic test has absolute diagnostic accuracy.

1. De Weck AL, Sanz ML, Gamboa PM, Aberer W, Sturm G, Bilo MB, et al. Diagnosis of immediate-type ßlactam allergy in vitro by flow-cytometric basophil activation test and sulfi doleukotriene production: a multicenter study. J Investig Allergol Clin Immunol 2009; 19: 91-109.

2. Dona I, Blanca-Lopez N, Torres M, Garcia-Campos J, Garcia-Nunez I, Gomez F, et al. Drug Hypersensitivity Reactions: Response patterns, Drug Involved, and Temporal Variations in a Large Series of Patients. J Investig Allergol Clin Immunol 2012; 22(5):363-371.

3. Garcia Nunez I, Barasona Villarajo M, Algaba Marmol M, Moreno Aguilar C, Guerra Pasadas F. Diagnosis of Patients with Immediate Hypersensitivity to β-Lactams Using Retest. J Investig Allergol Clin Immunol 2012;22(1):41-7.

4. Boumiza R, Debard A, Monneret G. The basophil activation test by flow cytometry: recent developents in clinical studies, standardisation and emerging perspectives.

Clin Mol Allergy 2005; 3:9.

5. Sanz ML, Gamboa PM, De Weck AL. Cellular Tests in the Diagnosis of Drug Hypersensitivity. Current Pharmaceutical Design 2008; 14: 2803-2808.

6. Thong BY, Mirakian R, Castells M, Pichler W, Romano A, Bonadonna P, et al. A world allergy organization international survey on diagnostic procedures and therapies in drug allergy/hypersensitivity. World Allergy Organ J. 2011;4(12):257-70.

7. Ebo DG, Leysen J, Mayorga C, Rozieres A, Knol E, Terreehorst I. The in vitro diagnosis of drug allergy: status and perspectives. Allergy 2011; 66:1275-1286.

8. Ebo DG, Hagendorns MM, Bridts C, Scherwegh A, De Clerck L, Stevens W. In vitro allergy diagnosis: should we follow the flow? Clin Exp Allergy 2004; 34: 332-339.

9. Demoly P, Piette V, Bousquet J. In vivo methods for study of allergy: skin tests, technique and interpretation.

In: Adkinson NF Jr, Yunginger JW, Busse WW, Bochner BS, Holgate TS, Simons FER, editors. Middleton’s Allergy, principles and practice, 6th ed. Philadelphia, Pennsylvania: Mosby, Inc. 2003; 631-643.

10. Natalia Hagău, Manuela Sfichi, Ramona Bologa, Simona Cocu, Cristina Indrei, Ionel Alb, et al. Basophil activation test using flow cytometry in the diagnostic of antibiotic allergy. Rev Romana Med Lab. 2010;18(4):47-53.

11. Bamber D. The area above the ordinal dominance graph and the area below the receiver operating characteristics graph. Journal of Mathematical Psychology 1975;12: 387-415.

12. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143: 29-36.

13. Mertes PM, Tajima K, Regnier-Kimmoun MA, Lambert M, Iohom G, Gueant-Rodriguez R, et al. Perioperative anaphylaxis. Med Clin N Am 2010; 94:761-789.

14. Ebo DG, Fisher MM, Hagendorens MM, Bridts CH, Stevens WJ. Anaphylaxis during anaesthesia: diagnostic approach. Allergy 2007: 62: 471-487.

15. Gamboa PM, Garcia-Aviles MC, Urrutia I, Antepara I, Esparza, Sanz ML. Basophil activation and sulfidoleukotriene production in patients with immediate allergy to betalactam antibiotics and negative skin tests. J Invest Allergol Clin Immunol 2004; 14: 278-283.

16. Romano A, Torres M, Castells M, Sanz M, Blanca M. Diagnosis and management of drug hypersensitivity reactions.

J Allergy Clin Immunol 2011; 127(3):S67-S73.

17. Mayorga C, Sanz ML, Gamboa PM, Garcia B. In vitro diagnosis of immediate allergic reactions to drugs: An update. J Investig Allergol Clin Immunol 2010;20(2):103-109.

18. Fontaine C, Mayorga C, Bousquet PJ, Arnoux B, Torres M, Blanca M, et al. Relevance of the determination of serum-specific IgE antibodies in the diagnosis of immediate βlactam allergy. Allergy 2007;62:47-52.

19. De Weck AL, Sanz ML, Gamboa PM, Aberer W, Bienvenu J, Blanca M, et al. Diagnostic Tests Based on Human Basophils: More Potentials and Perspectives than Pitfalls.

II. Techincal Issues. J Investig Allergol Clin Immunol 2008; 18(3): 143-155.

20. Torres MJ, Padial A, Mayorga C, Fernandez T, Sanchez-Sabate E, Cornejo-Garcia J, et al. The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams. Clin Exp Allergy 2004;34:1768-1775.

21. Sanz ML, Gamboa PM, Antepara I, Uasuf C, Vila L, Garcia-Aviles C, et al. Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate- type reactions to betalactam antibiotics. Clin Exp All 2002;32: 277-286.

22. Ebo DG, Sainte-Laudy J, Bridts CH, Mertens CH, Hagendorens MM, Schuerwegh AJ, et al. Flow-assisted allergy diagnosis: current applications and future perspectives.

Allergy 2006: 61: 1028-1039.

23. Abuaf N, Rostane H, Rajoely B, Gaouarw H, Autegardenw JE, Leynadierw F, et al. Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy. Clinical and Experimental Allergy 2008;38: 921-928.

24. Fernandez TD, Torres MJ, Blanca-Lopez N. Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins. Allergy 2009;64:242-248.

25. Silva R, Cruz L, Bothelo C, Cadinha S, Castro E, Rodrigues J, et al. Work up of patients with history of beta-lactam hypersensitivity. Allergol Immunopathol 2009;37(4):193-197.

26. Romano A, Ventura M. Advances in Diagnosing Drug Hypersensitivity reactions. Current Pharmaceutical Design 2008; 14(27): 2767-2769.

27. Blanca M, Romano A, Torres MJ, Fernandez J, Mayorga C, Rodriguez J, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy 2009; 64:183-193.

28. Brockow K, Garvey L, Aberer W, Atanaskovic- Markovic M, Barbaud A, Bilo M, et al. Skin test concentrations for systemically administered drugs- an ENDA/EAACI Drug Allergy Interest Group position paper.

Allergy 2013; 68:702-712.

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information

IMPACT FACTOR 2018: 0,800
5-year IMPACT FACTOR: 0,655

CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2018: 0.194
Source Normalized Impact per Paper (SNIP) 2018: 0.306


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 200 129 9
PDF Downloads 74 61 8