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The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition

The high prevalence of allergy to β-lactam antibiotics is a worldwide issue. Accuracy of diagnostic methods is important to prove tolerance or allergy, with skin test considered the best validated in vivo method for diagnosing immediate reactions to β-lactams. Although drug provocation test is the r...

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Autores principales: Mayorga, Cristobalina, Montañez, Maria I., Najera, Francisco, Bogas, Gador, Fernandez, Tahía D., Gil, David Rodríguez, Palacios, Ricardo, Torres, Maria J., Vida, Yolanda, Perez-Inestrosa, Ezequiel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952312/
https://www.ncbi.nlm.nih.gov/pubmed/33716734
http://dx.doi.org/10.3389/fphar.2021.585890
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author Mayorga, Cristobalina
Montañez, Maria I.
Najera, Francisco
Bogas, Gador
Fernandez, Tahía D.
Gil, David Rodríguez
Palacios, Ricardo
Torres, Maria J.
Vida, Yolanda
Perez-Inestrosa, Ezequiel
author_facet Mayorga, Cristobalina
Montañez, Maria I.
Najera, Francisco
Bogas, Gador
Fernandez, Tahía D.
Gil, David Rodríguez
Palacios, Ricardo
Torres, Maria J.
Vida, Yolanda
Perez-Inestrosa, Ezequiel
author_sort Mayorga, Cristobalina
collection PubMed
description The high prevalence of allergy to β-lactam antibiotics is a worldwide issue. Accuracy of diagnostic methods is important to prove tolerance or allergy, with skin test considered the best validated in vivo method for diagnosing immediate reactions to β-lactams. Although drug provocation test is the reference standard, it cannot be performed in highly risk reactions or in those with positive skin tests. For skin tests, the inclusion of major and minor determinants of benzylpenicillin (BP) is recommended. Commercial skin test reagents have changed along time, including as minor determinants benzylpenicillin, benzylpenicilloate (BPO), and benzylpenilloate (PO). Major determinants consists of multivalent conjugates of benzylpenicilloyl coupled through amide bond to a carrier polymer, such as penicilloyl-polylysine (PPL) or benzylpenicilloyl-octalysine (BP-OL). The chemical stability of such reagents has influenced the evolution of the composition of the commercial kits, as this requirement is necessary for improving the quality and standardization of the product. In this work, we provide a detailed study of the chemical stability of BP determinants. We observed that those structures suffer from an epimerization process in C-5 at different rates. Butylamine-Benzylpenicilloyl conjugates (5R,6R)-Bu-BPO and (5S,6R)-Bu-BPO were selected as a simple model for mayor determinant to evaluate the role of the different epimers in the immunoreactivity with sera from penicillin-allergic patients. In vitro immunoassays indicate that any change in the chemical structure of the antigenic determinant of BP significantly affects IgE recognition. The inclusion of stereochemically pure compounds or mixtures may have important implications for both the reproducibility and sensitivity of in vivo and in vitro diagnostic tests.
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spelling pubmed-79523122021-03-13 The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition Mayorga, Cristobalina Montañez, Maria I. Najera, Francisco Bogas, Gador Fernandez, Tahía D. Gil, David Rodríguez Palacios, Ricardo Torres, Maria J. Vida, Yolanda Perez-Inestrosa, Ezequiel Front Pharmacol Pharmacology The high prevalence of allergy to β-lactam antibiotics is a worldwide issue. Accuracy of diagnostic methods is important to prove tolerance or allergy, with skin test considered the best validated in vivo method for diagnosing immediate reactions to β-lactams. Although drug provocation test is the reference standard, it cannot be performed in highly risk reactions or in those with positive skin tests. For skin tests, the inclusion of major and minor determinants of benzylpenicillin (BP) is recommended. Commercial skin test reagents have changed along time, including as minor determinants benzylpenicillin, benzylpenicilloate (BPO), and benzylpenilloate (PO). Major determinants consists of multivalent conjugates of benzylpenicilloyl coupled through amide bond to a carrier polymer, such as penicilloyl-polylysine (PPL) or benzylpenicilloyl-octalysine (BP-OL). The chemical stability of such reagents has influenced the evolution of the composition of the commercial kits, as this requirement is necessary for improving the quality and standardization of the product. In this work, we provide a detailed study of the chemical stability of BP determinants. We observed that those structures suffer from an epimerization process in C-5 at different rates. Butylamine-Benzylpenicilloyl conjugates (5R,6R)-Bu-BPO and (5S,6R)-Bu-BPO were selected as a simple model for mayor determinant to evaluate the role of the different epimers in the immunoreactivity with sera from penicillin-allergic patients. In vitro immunoassays indicate that any change in the chemical structure of the antigenic determinant of BP significantly affects IgE recognition. The inclusion of stereochemically pure compounds or mixtures may have important implications for both the reproducibility and sensitivity of in vivo and in vitro diagnostic tests. Frontiers Media S.A. 2021-02-26 /pmc/articles/PMC7952312/ /pubmed/33716734 http://dx.doi.org/10.3389/fphar.2021.585890 Text en Copyright © 2021 Mayorga, Montañez, Najera, Bogas, Fernandez, Gil, Palacios, Torres, Vida, Perez-Inestrosa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Mayorga, Cristobalina
Montañez, Maria I.
Najera, Francisco
Bogas, Gador
Fernandez, Tahía D.
Gil, David Rodríguez
Palacios, Ricardo
Torres, Maria J.
Vida, Yolanda
Perez-Inestrosa, Ezequiel
The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
title The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
title_full The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
title_fullStr The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
title_full_unstemmed The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
title_short The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition
title_sort role of benzylpenicilloyl epimers in specific ige recognition
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952312/
https://www.ncbi.nlm.nih.gov/pubmed/33716734
http://dx.doi.org/10.3389/fphar.2021.585890
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