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Molecules 2018, 23(5), 997; https://doi.org/10.3390/molecules23050997

Dendrimeric Antigens for Drug Allergy Diagnosis: A New Approach for Basophil Activation Tests

1
Departamento de Química Orgánica, Universidad de Málaga—IBIMA, 29071 Málaga, Spain
2
Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnológico de Andalucía, 29590 Málaga, Spain
3
Research Laboratory, IBIMA—Regional University Hospital of Málaga—UMA, 29009 Málaga, Spain
4
Allergy Unit, IBIMA—Regional University Hospital of Málaga—UMA, 29009 Málaga, Spain
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Ashok Kakkar
Received: 5 March 2018 / Revised: 6 April 2018 / Accepted: 20 April 2018 / Published: 24 April 2018
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Abstract

Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens. Structural features of benzylpenicilloyl-DeAn and amoxicilloyl-DeAn (G2 and G4 PAMAM) were studied by diffusion Nuclear Magnetic Resonance (NMR) experiments and are discussed in relation to molecular dynamics simulation (MDS) observations. IgE recognition was clinically evaluated using the basophil activation test (BAT) for allergic patients and tolerant subjects. Diffusion NMR experiments, MDS and cellular studies provide evidence that the size of the DeAn, its antigen composition and tridimensional distribution play key roles in IgE-antigen recognition at the effector cell surface. These results indicate that the fourth generation DeAns induce a higher level of basophil activation in allergic patients. This approach can be considered as a potential complementary diagnostic method for evaluating penicillin allergy. View Full-Text
Keywords: PAMAM; dendrimeric antigens; penicillin; drug allergy; basophil activation tests PAMAM; dendrimeric antigens; penicillin; drug allergy; basophil activation tests
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Molina, N.; Martin-Serrano, A.; Fernandez, T.D.; Tesfaye, A.; Najera, F.; Torres, M.J.; Mayorga, C.; Vida, Y.; Montañez, M.I.; Perez-Inestrosa, E. Dendrimeric Antigens for Drug Allergy Diagnosis: A New Approach for Basophil Activation Tests. Molecules 2018, 23, 997.

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