Recognition of multiepitope dendrimeric antigens by human immunoglobulin E

Montañez, María Isabel; Nájera, Francisco; Mayorga, Cristobalina; Ruiz-Sánchez, Antonio J.; Vida, Yolanda; Collado, Daniel; Blanca, Miguel; Torres, Marı́a José; Pérez‐Inestrosa, Ezequiel

doi:10.1016/j.nano.2015.01.006

Cited by 18 publications

(38 citation statements)

References 41 publications

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“…The relevance of the AX side chain in IgE recognition has been recently corroborated in a study that investigated the influence of the tridimensional conformation of BP and AX on IgE recognition using synthetic nano‐carriers . Differences in spatial conformation were found, with the benzylpenicilloyl (BPO) group partially exposed to IgE recognition, as the benzyl side chain was oriented inside the carrier molecule, whereas the entire structure of the AXO group was outside of the carrier molecule .…”

Section: Ige Recognition Studiesmentioning

confidence: 83%

“…Using the same approach with AX, it was demonstrated that the majority of the generated monoclonal antibodies recognized an epitope in which the side chain was a major constituent, although with variable contributions from other regions of the molecule . The relevance of the AX side chain in IgE recognition has been recently corroborated in a study that investigated the influence of the tridimensional conformation of BP and AX on IgE recognition using synthetic nano‐carriers . Differences in spatial conformation were found, with the benzylpenicilloyl (BPO) group partially exposed to IgE recognition, as the benzyl side chain was oriented inside the carrier molecule, whereas the entire structure of the AXO group was outside of the carrier molecule .…”

Section: Ige Recognition Studiesmentioning

confidence: 94%

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The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

Torres

Montañez

Ariza

et al. 2016

Clin Experimental Allergy

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Betalactam (BL) antibiotics are the drugs most frequently involved in IgE-mediated reactions. The culprit BL varies according to consumption patterns, with amoxicillin (AX) more prevalent in Southern Europe and penicillin V in Scandinavian countries. Nowadays, the combination of AX and clavulanic acid (CLV) is the most highly consumed BL containing medicine worldwide. Both BLs, AX and CLV, can independently be involved in reactions, which poses a diagnostic challenge. In patients with immediate allergic reactions to AX, two patterns of responses have been described, those responding to benzylpenicillin (cross-reactors) and those selective to AX. In addition, selective reactions to CLV account for around 30% of allergic reactions to the combination AX-CLV. These patterns of IgE recognition could be related to differences in the haptenation process, in the immunological response, or in the BL involved in the first sensitization. In this regard, patients with selective responses to CLV are generally younger than those allergic to AX or benzylpenicillin. So far, no evidence of cross-reactivity between CLV and other BLs has been reported. This shows the importance of an accurate diagnosis of CLV allergy, as patients with selective reactions to CLV could take other BLs including AX. Diagnosis can be performed in vivo and in vitro, although no immunoassay currently exists. Research regarding the CLV antigenic determinants and protein conjugates is essential to improve diagnosis. BLs need to covalently bind to a carrier protein to be immunogenic. The antigenic determinant of AX is the amoxicilloyl amide, but CLV leads to unstable structures, many of which are unknown. Moreover, the nature of the BL-protein conjugates plays an important role in IgE recognition. This review aims to summarize current knowledge on the immunochemistry, diagnostic approaches as well as chemical and proteomic studies for both AX and CLV.

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Section: Ige Recognition Studiesmentioning

confidence: 83%

Section: Ige Recognition Studiesmentioning

confidence: 94%

The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

Torres

Montañez

Ariza

et al. 2016

Clin Experimental Allergy

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“…In the particular field of drug allergy, immunoassays are of special importance since they are the most widely employed method for the detection and quantification of specific antibodies to the drugs in blood sera . Our research group has a strong background in the development of functional materials for immunoassays with applications for in vitro diagnosis of allergy to β‐lactam antibiotics by the determination of specific IgE antibodies . Different kinds of immunoassays have been explored for this purpose, being the radioallergosorbent test (RAST) the most employed due to its high sensitivity .…”

Section: Figurementioning

confidence: 99%

“…For this proof of concept, one synthetically simple dendrimeric structure of generation 1 of BAPAD haptenized with amoxicillin was chosen. The reactivity of penicillins with nucleophiles is well established and is usually employed to haptenize different kind of carriers . The amoxicilloyl group (AXO) is the hapten obtained from amoxicillin, given a haptenized BAPAD structure from the nucleophilic attack of the superficial amine groups by the cleavage of the β‐lactam ring of amoxicillin.…”

Section: Figurementioning

confidence: 99%

Naphthalimide Dyes with Orthogonal Functional Groups for “Click” Chemistry: Attachment to Solid Supports and Applications in Drug Allergy Diagnosis

et al. 2020

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The preparation and characterization of new functional materials for sensing have an important role in clinical diagnosis. Monitoring the surface functionalization of functional material is crucial because the final sensing properties are affected by how the (bio)molecules are immobilized on the surface of solid supports. Here, a new approach for the preparation of functional materials for biomedical diagnosis was developed. This method employs a fluorescent dye comprising 4‐amino‐1,8‐naphthalimide with two orthogonal functional groups suitable for click chemistry. The orthogonal reactivity of these groups allows the sequential functionalization of the fluorophore, firstly with (bio)molecules, and then binding of the (bio)molecule‐naphthalimide macrostructure onto the surface of a solid support. The fluorescent properties confirm the immobilization of the (bio)molecule on the surface of the solid support, without requiring other indirect methods to verify the immobilization. These functional materials were tested successfully with sera of patients, thus proving their potential application for allergic drug diagnosis.

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“…In many cases, in vitro tests for diagnosis are necessary due to the risk of performing provocation tests. In vitro tests employ complexes of the drugs of interest with serum albumin or with electrophilic amino acids, synthetic polymers or nanostructures to probe the antibodies present in the patients' sera or to perform cellular activation assays [9,10]. Nevertheless, these structures may not represent the endogenous antigens and result in false negatives or low sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies

González-Morena¹,

Montanez²,

Aldini³

et al. 2017

CPD

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Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be life-threatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions. Nevertheless, non-covalent interactions of drugs with receptors in immune cells or with MHC clefts and/or exposed peptides can also play an important role. In recent years, development of proteomic approaches has allowed the identification and characterization of the protein targets for modification by drugs in vivo and in vitro, the nature of peptides exposed on MHC molecules, the changes in protein levels induced by drug treatment, and the concomitant modifications induced by danger signals, thus providing insight into context factors. Nevertheless, given the complexity and multifactorial nature of drug hypersensitivity reactions, understanding the underlying mechanisms also requires the integration of knowledge from genomic, metabolomic and clinical studies.

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Recognition of multiepitope dendrimeric antigens by human immunoglobulin E

Cited by 18 publications

References 41 publications

The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

Naphthalimide Dyes with Orthogonal Functional Groups for “Click” Chemistry: Attachment to Solid Supports and Applications in Drug Allergy Diagnosis

Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies

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