RT Journal Article
T1 Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions.
A1 Fernandez-Santamaria, Ruben
A1 Bogas, Gador
A1 Montañez, Maria Isabel
A1 Ariza, Adriana
A1 Salas, Maria
A1 Cespedes, Jose Antonio
A1 Labella, Marina
A1 Paris, Juan Luis
A1 Perez-Sanchez, Natalia
A1 Perez-Inestrosa, Ezequiel
A1 Vida, Yolanda
A1 Fernandez, Tahia D
A1 Mayorga, Cristobalina
A1 Torres, Maria Jose
K1 Antigenic determinants
K1 Clavulanic acid
K1 Immediate drug hypersensitivity reactions
K1 Maturation
K1 Proliferation
AB 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. 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. 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%. 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.
PB John Wiley and Sons
YR 2022
FD 2022-09-28
LK http://hdl.handle.net/10668/19901
UL http://hdl.handle.net/10668/19901
LA en
NO Fernandez-Santamaria R, Bogas G, Montañez MI, Ariza A, Salas M, Cespedes JA, et al. Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions. Allergy. 2022 Oct;77(10):3070-3083.
NO This work has been supported by Institute of Health ‘Carlos III’ (ISCIII) of the Ministry of Economy and Competitiveness (MINECO) (grants co- funded by European Regional Development Fund: PI15/01206, PI17/01237, PI18/00095, PI20/01734, RETICS ARADYAL RD16/0006/0001); Andalusian Regional Ministry of Health (grants PI- 0241- 2016, PE- 0172- 2018, PI- 0127- 2020); Spanish Ministerio de Ciencia e Innovación (Proyectos de I+D+I «Programación Conjunta Internacional», EuroNanoMed 2019 (PCI2019- 111825- 2), Ministerio de Ciencia y Educación (PID2019- 104293GB- I00), I nstituto de Salud Carlos III (ISCIII) of MINECO (RD16/0006/0012), Junta de Andalucía ( PY20_00384 ). AA and NPS hold Senior Postdoctoral Contracts (RH- 0099- 2020 and RH- 0085- 2020) from Andalusian Regional Ministry of Health (cofunded by European Social Fund (ESF): ‘Andalucía se mueve con Europa’). JLP holds a Sara Borrell fellowship (CD19/00250) by ISCIII of MINECO (cofunded by ESF, “El FSE invierte en futuro”). GB holds a ‘Juan Rodes’ contract (JR18/00054) by ISCIII of MINECO (cofunded by ESF). MIM holds a ‘Miguel Servet II’ grant (CPII20/00028) by ISCIII of MINECO (cofunded by ESF). ML holds a ‘Rio Hortega’ contract (CM20/00210) by ISCIII of MINECO (cofunded by ESF). CM holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health (RC- 0004- 2021). NMR experiments for characterizing molecule structures have been performed in the ICTS ‘NANBIOSIS’, by the U28 Unit at the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND).
DS RISalud
RD Aug 8, 2025