Montanez, Mara I.; Najera, Francisco; Mayorga, Cristobalina; Ruiz-Sanchez, Antonio J.; Vida, Yolanda; Collado, Daniel; Blanca, Miguel; Torres, Maria J.; Perez-Inestrosa, Ezequiel
Recognition of multiepitope dendrimeric antigens by human immunoglobulin E
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 11:579-588, APR 2015

In vitro drug allergy tests have limited sensitivity, partly due to a poor understanding of the immunological recognition of in vitro drug-protein conjugates. We have designed and synthesized multivalent mono- and bi-epitope dendrimeric antigen (DeAn) conjugates and studied their chemical and tridimensional structures. We describe differences in the spatial distribution and conformation of these conjugated epitopes for the first time: a partially hidden benzylpenicilloyl and amore exposed amoxicilloyl. Our data suggest that DeAn conjugates provide a useful model for studying IgE recognition in patients who suffer from an allergic reaction to benzylpenicillin and/or amoxicillin. 1D and 2D NMR, MDS and immunochemical studies provide evidence that both antigen composition and tridimensional distribution play key roles in IgE-antigen recognition. Bi-epitope DeAn conjugates could potentially allow the diagnosis of patients allergic to any of these two drugs with a single test and represent the basis for a broadly-applicable in vitro assay. From the Clinical Editor: The prevalence of allergic drug reactions is rising and there is an imperative need to identify patients at risk. In this interesting and important article, the authors developed a novel method for detecting drug specific IgE antibodies, responsible for allergic reactions, by using multivalent mono-and bi-epitope Dendrimeric Antigen (DeAn) conjugates. The continued success of this research may pave way of eventual development of a simple diagnostic test. (C) 2015 Elsevier Inc. All rights reserved.

DOI:10.1016/j.nano.2015.01.006

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