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

Autor: Amene Tesfaye, Yolanda Vida, Noemi Molina, Angela Martin-Serrano, Ezequiel Perez-Inestrosa, María José Torres, Maria I. Montañez, Cristobalina Mayorga, Francisco Najera, Tahia D. Fernandez
Přispěvatelé: [Molina,N, Najera,F, Vida,Y, Perez-Inestrosa,E] Departamento de Química Orgánica, Universidad de Málaga—IBIMA, Málaga, Spain. [Molina,N, Martin-Serrano,A, Fernandez,TD, Tesfaye,A, Torres,MJ, Mayorga,C, Montañez,MI, Perez-Inestrosa,E] Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnológico de Andalucía, Málaga, Spain. [Martin-Serrano,A, Fernandez,TD, Tesfaye,A, Montañez,MI] Research Laboratory, IBIMA—Regional University Hospital of Málaga—UMA, Málaga, Spain. [Torres,MJ, Mayorga,C] Allergy Unit, IBIMA—Regional University Hospital of Málaga—UMA,Málaga, Spain, The present study has been supported by State Secretariat for Research, Development and Innovation of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF)): MINECO CTQ2016-75870P, by Institute of Health 'Carlos III' (ISCIII) of MINECO (grants cofunded by ERDF): PI12/02529, PI15/01206, CP15/00103, PI17/01237, RETICs RIRAAF RD12/0013/0001 and 0003 and RETIC ARADYAL RD16/0006/0001 and 0012, by Andalusian Regional Ministry of Economy and Knowledge (grants cofunded by ERDF): CTS-06603, by Andalusian Regional Ministry Health (grants: PI-0699-2011, PI-0179-2014, PI-0241-2016 and PI-0250-2016), and 'Premio UNICAJA a la innovación en biomedicina y salud'. NM holds a FPU grant of MECD (FPU15/00641). TDF hold a 'Ramon y Cajal' research contract from MINECO (RYC-2013-13138). AT has received funding from the European Union’s H2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 713721. CM holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. MIM holds a 'Miguel Servet I' (CP15/00103) contract by ISCIII of MINECO (grants cofunded by European Social Fund (ESF)). Partially supported by Open Access Funds from 'Universidad de Málaga'.
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Models
Molecular
Magnetic Resonance Spectroscopy
Pharmaceutical Science
Basophil
PAMAM
Immunoglobulin E
Epitope
Analytical Chemistry
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay [Medical Subject Headings]
Epitopes
Drug Discovery
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models
Theoretical::Models
Molecular [Medical Subject Headings]
dendrimeric antigens
Immunoassay
Prueba de desgranulación de los Basófilos
biology
medicine.diagnostic_test
Chemistry
penicillin
drug allergy
basophil activation tests
Penicilinas
Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings]
3. Good health
Basophils
Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings]
medicine.anatomical_structure
Chemistry (miscellaneous)
Molecular Medicine
Hipersensibilidad a las drogas
Cell activation
Dendrimers
Drug allergy
Penicillins
Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Structure-Activity Relationship [Medical Subject Headings]
Article
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques
Analytical::Spectrum Analysis::Magnetic Resonance Spectroscopy [Medical Subject Headings]
Drug Hypersensitivity
lcsh:QD241-441
03 medical and health sciences
Structure-Activity Relationship
Antigen
lcsh:Organic chemistry
medicine
Humans
Physical and Theoretical Chemistry
Organic Chemistry
Allergens
Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins [Medical Subject Headings]
medicine.disease
Basophil activation
030104 developmental biology
Immunology
biology.protein
Chemicals and Drugs::Biological Factors::Antigens::Allergens [Medical Subject Headings]
Chemicals and Drugs::Macromolecular Substances::Polymers::Dendrimers [Medical Subject Headings]
Anatomy::Cells::Myeloid Cells::Granulocytes::Basophils [Medical Subject Headings]
Zdroj: Molecules, Vol 23, Iss 5, p 997 (2018)
Molecules
Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules; Volume 23; Issue 5; Pages: 997
ISSN: 1420-3049
Popis: 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. Yes
Databáze: OpenAIRE
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