RT Journal Article
T1 Identification of an antigenic determinant of clavulanic acid responsible for IgE-mediated reactions.
A1 Barbero, Nekane
A1 Fernández-Santamaría, Rubén
A1 Mayorga, Cristobalina
A1 Martin-Serrano, Ángela
A1 Salas, María
A1 Bogas, Gador
A1 Nájera, Francisco
A1 Pérez-Sala, Dolores
A1 Pérez-Inestrosa, Ezequiel
A1 Fernandez, Tahia D
A1 Montañez, María I
A1 Torres, María J
K1 IgE
K1 basophils
K1 clavulanic acid
K1 drug allergy
K1 immediate reactions
K1 in vitro test
AB Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin-CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis. Based on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD-I (N-protein, 3-oxopropanamide) and AD-II (N-protein, 3-aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches. Two synthetic analogs of AD-I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLV-treated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls. We have identified AD-I as one CLV antigenic determinant, which is the drug fragment that remains protein-bound.
YR 2019
FD 2019-04-04
LK http://hdl.handle.net/10668/13656
UL http://hdl.handle.net/10668/13656
LA en
DS RISalud
RD Apr 6, 2025