Neo-antigens for the serological diagnosis of IgE-mediated drug allergic reactions to antibiotics cephalosporin, carbapenem and monobactam

Edurne Peña-Mendizabal,Ángel Maquieira,Sergi Morais

doi:10.1038/s41598-020-73109-w

Edurne Peña-Mendizabal, Ángel Maquieira + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-73109-w

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Abstract

New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for β-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty β-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-β-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-β-lactam IgE antibodies with high sensitivity (< 0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of β-lactam antibiotics renders improved molecular recognition events when the 4-member β-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.

Highlights

New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for β-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam
Several prospective studies are found in the literature that have evaluated the use of cephalosporins4,5,19,20, carbapenems[21] or monobactams in patients with documented penicillin allergy who require BLC treatment, but very few in vitro assays are available for these s tudies[3]
Unlike all the studies related to penicillins reactivity, in which the chemical structures of their antigenic determinants are already established, the chemistry of other β-lactam antibiotics lacks this information

Summary

Introduction

New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for β-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. These findings reveal that the haptenisation of β-lactam antibiotics renders improved molecular recognition events when the 4-member β-lactam ring remains unmodified, and may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam. BLC allergic reactions caused by minor determinants have been considered extremely important in penicillin allergies; e.g., in skin tests for diagnosing β-lactam allergy[17], and have been associated with specific systemic anaphylaxis[18] For this reason, it is necessary to systematically and clinically study the relevance and relative importance of these -llanyl derivatives as a new range of ‘minor’ determinants for β-lactam a llergy[13]. It is important to retain the functional groups that are unique to hapten[26]

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