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

Noemi Molina,Angela Martin-Serrano,Cristobalina Mayorga,Francisco Najera,Yolanda Vida,Tahia Fernandez,Ezequiel Perez-Inestrosa,María Torres,Amene Tesfaye,Maria Montañez

doi:10.3390/molecules23050997

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.

Highlights

Dendrimers are highly branched and regular macromolecules with well-defined structures that attract considerable interest due to their potential applications in many fields of science.The three-dimensional architecture of dendrimeric systems confers them various intrinsic features such as structural homogeneity, integrity, controlled composition and high-density multidentate homogeneous terminal groups, ready for conjugation
We evaluated whether the inclusion of these Dendrimeric Antigens (DeAns) can improve the potential of basophil activation test (BAT) for diagnosing penicillin allergic patients
We evaluated the ability of these nanostructures to stimulate basophils and we found that DeAns were able to induce activation in a selective and specific way

Summary

Introduction

Dendrimers are highly branched and regular macromolecules with well-defined structures that attract considerable interest due to their potential applications in many fields of science. The three-dimensional architecture of dendrimeric systems confers them various intrinsic features such as structural homogeneity, integrity, controlled composition and high-density multidentate homogeneous terminal groups, ready for conjugation. These characteristics, added to their stability and versatility, mean that dendrimers have been used for many applications, such as sensing, catalysis, molecular electronics and photonics [1]. One important application is related to the study of allergic drug reactions. Allergic drug reactions are one of the most important health problems nowadays.

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