title: Recognition of multiepitope dendrimeric antigens by human immunoglobulin E.
abstract: 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 a more 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.
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors: María I
authors: MI
authors: Montañez
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Department of Organic Chemistry, IBIMA, University of Malaga, Malaga, Spain.
authors: Francisco
authors: F
authors: Najera
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors: Cristobalina
authors: C
authors: Mayorga
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Department of Organic Chemistry, IBIMA, University of Malaga, Malaga, Spain.
authors: Antonio J
authors: AJ
authors: Ruiz-Sanchez
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Department of Organic Chemistry, IBIMA, University of Malaga, Malaga, Spain.
authors: Yolanda
authors: Y
authors: Vida
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Department of Organic Chemistry, IBIMA, University of Malaga, Malaga, Spain.
authors: Daniel
authors: D
authors: Collado
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors: Miguel
authors: M
authors: Blanca
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors: María J
authors: MJ
authors: Torres
authors: BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnologico de Andalucia, Malaga, Spain; Department of Organic Chemistry, IBIMA, University of Malaga, Malaga, Spain. Electronic address: inestrosa@uma.es.
authors: Ezequiel
authors: E
authors: Perez-Inestrosa
mesh_terms: D000658:Amoxicillin / Q000737:chemistry* / Q000276:immunology; D050091:Dendrimers / Q000737:chemistry*; D004342:Drug Hypersensitivity / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry* / Q000276:immunology; D008297:Male; D010400:Penicillin G / Q000737:chemistry* / Q000276:immunology
chemical_list: D050091:Dendrimers; D000939:Epitopes; C104700:PAMAM Starburst; D007073:Immunoglobulin E; D000658:Amoxicillin; D010400:Penicillin G
keywords: Allergy; Dendrimer; Immune response; Immunochemistry; In vitro test; Molecular modeling