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Basophil Histamine Release Induced by Amoxicilloyl-poly-L-lysine Compared With Amoxicillin in Patients With IgE-Mediated Allergic Reactions to Amoxicillin

Arribas F1, Falkencrone S2, Sola J3, Gomez-Serranillos MP4, Laguna JJ5, Montañez MI6,7, Fernandez TD6,7, Rodríguez D1, Pineda F1, Skov PS2, Mayorga C6,7*, MJ Torres6,7*

*Both authors contributed equally
1Diater Laboratorios, Madrid, Spain
2Department of Dermatology, University Hospital of Odense, Denmark and Charité, Berlin, Germany
3Allergy Service, Ramon y Cajal Hospital, Madrid, Spain
4Departament of Pharmacology, University Complutense of Madrid, Spain
5Allergy Unit, Cruz Roja Hospital, Madrid, Spain
6Allergy Unit, IBIMA-Regional University Hospital of Malaga UMA, Málaga, Spain
7Andalusian Center for Nanomedicine and Biotechnology - BIONAND, Málaga, Spain

J Investig Allergol Clin Immunol 2017; Vol 27(6) : 356-362
doi: 10.18176/jiaci.0180

Background: Amoxicillin (AX) is the ß-lactam most often involved in IgE-mediated reactions. Diagnosis is based mainly on skin testing, although sensitivity is not optimal. We produced a new AX derivative, amoxicilloyl-poly-L-lysine (APL), and analyzed its recognition of IgE using the passive histamine release test (pHRT).
Methods: The study population comprised patients (n=19) with confirmed AX allergy and specific IgE to AX and controls (n=10) with good tolerance to AX. pHRT was performed using “IgE-stripped” blood from a single donor that was sensitized in vitro by patient sera and incubated with AX or APL. Histamine release was determined and expressed as nanograms of histamine released per milliliter of blood.
Results: The clinical symptoms were anaphylaxis (n=9), urticaria (n=7), erythema (n=2), and nondefined immediate reactions (n=1). The median (IQR) time interval between reaction and study was 90 (60-240) days and between drug intake and development of symptoms 24 (10-60) minutes. The median sIgE level was 3.37 (0.95-5.89) kUA/L. The sensitivity of pHRT to APL was 79% and the specificity 100%, which were higher than data obtained with pHRT to AX (63% sensitivity and 90% specificity). There was a positive correlation between maximal histamine release levels obtained with AX and APL (r=0.63).
Conclusions: In patients with immediate hypersensitivity reactions to AX, APL showed higher sensitivity and specificity than the culprit drug, AX, when tested in vitro by pHRT. This indicates that APL can improve the in vitro diagnostic accuracy of allergic reactions to AX. Further assessment of skin testing is necessary.

Key words: Allergy, Amoxicillin, Amoxicilloyl-poly-L-lysine, Basophil histamine release, Immediate reactions