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Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions
Author(s) -
FernandezSantamaria Ruben,
Bogas Gador,
Montañez Maria Isabel,
Ariza Adriana,
Salas Maria,
Cespedes Jose Antonio,
Labella Marina,
Paris Juan Luis,
PerezSanchez Natalia,
PerezInestrosa Ezequiel,
Vida Yolanda,
Fernandez Tahia D.,
Mayorga Cristobalina,
Torres Maria Jose
Publication year - 2022
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.15383
Subject(s) - flow cytometry , antigen , in vitro , immune system , immunology , cell growth , dendritic cell , t cell , cell , chemistry , medicine , biochemistry
Background Immediate drug hypersensitivity reactions (IDHRs) to clavulanic acid (CLV) have increased in the last decades due to a higher consumption alongside amoxicillin (AX). Due to its chemical instability, diagnostic procedures to evaluate IDHRs to CLV are difficult, and current in vitro assays do not have an optimal sensitivity. The inclusion of the specific metabolites after CLV degradation, which are efficiently recognised by the immune system, could help to improve sensitivity of in vitro tests. Methods Recognition by dendritic cells (DCs) of CLV and the synthetic analogues of two of its hypothesised antigenic determinants (ADs) was evaluated by flow cytometry in 27 allergic patients (AP) and healthy controls (HC). Their ability to trigger the proliferation of T cells was also analysed by flow cytometry. Results The inclusion of synthetic analogues of CLV ADs, significantly increased the expression of maturation markers on DCs from AP compared to HC. A different recognition pattern could be observed with each AD, and, therefore, the inclusion of both ADs achieves an improved sensitivity. The addition of synthetic ADs analogues increased the proliferative response of CD4 + Th2 compared to the addition of native CLV. The combination of results from both ADs increased the sensitivity of proliferative assays from 19% to 65% with a specificity higher than 90%. Conclusions Synthetic ADs from CLV are efficiently recognised by DCs with ability to activate CD4 + Th2 cells from AP. The combination of analogues from both ADs, significantly increased the sensitivity of DC maturation and T‐cell proliferation compared to native CLV.