Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions.
Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions.
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DOI：
10.1111/all.15383
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发表时间：
2022-10
期刊：
影响因子：
12.4
通讯作者：
Torres, Maria Jose
中科院分区：
文献类型：
--
作者：
Fernandez-Santamaria, Ruben;Bogas, Gador;Montanez, Maria Isabel;Ariza, Adriana;Salas, Maria;Cespedes, Jose Antonio;Labella, Marina;Paris, Juan Luis;Perez-Sanchez, Natalia;Perez-Inestrosa, Ezequiel;Vida, Yolanda;Fernandez, Tahia D.;Mayorga, Cristobalina;Torres, Maria Jose
关键词：
过去几十年来，由于与阿莫西林 (AX) 一起使用的量增加，克拉维酸 (CLV) 的立即药物过敏反应 (IDHR) 有所增加。由于其化学不稳定性，评估 IDHR 对 CLV 的诊断程序很困难，并且当前的体外测定不具有最佳灵敏度。 CLV 降解后包含可被免疫系统有效识别的特定代谢物，有助于提高体外测试的灵敏度。通过流式细胞术在 27 名过敏患者 (AP) 和健康对照 (HC) 中评估了 CLV 的树突状细胞 (DC) 及其两个假设的抗原决定簇 (AD) 的合成类似物的识别能力。还通过流式细胞术分析了它们触发 T 细胞增殖的能力。与 HC 相比，包含 CLV AD 的合成类似物显着增加了 AP 的 DC 上成熟标志物的表达。每个 AD 都可以观察到不同的识别模式，因此，包含两个 AD 可以提高灵敏度。与添加天然 CLV 相比，添加合成 AD 类似物增强了 CD4+Th2 的增殖反应。两种 AD 结果的结合将增殖检测的灵敏度从 19% 提高到 65%，特异性高于 90%。来自 CLV 的合成 AD 可被 DC 有效识别，并能够激活来自 AP 的 CD4+Th2 细胞。与天然 CLV 相比，两种 AD 类似物的组合显着提高了 DC 成熟和 T 细胞增殖的敏感性。 CLV 合成抗原决定簇（AD-I 和 AD-II）可被 CLV 过敏患者的 moDC 有效识别。一些 CLV-AD 诱导过敏患者 moDC 上激活、成熟和迁移标志物的表达。用一些 CLV-AD 预刺激 moDC 会诱导 CD4+Th2 细胞增殖。不同 CLV-AD 类似物的结果组合将 LTT 敏感性提高至 65%。缩写：ADs，抗原决定簇； CCR7，7 型 C-C 趋化因子受体； CLV，克拉维酸； LTT，淋巴细胞转化试验； moDC，单核细胞衍生的树突状细胞
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. CLV synthetic antigenic determinants (AD‐I and AD‐II) are efficiently recognised by moDCs from CLV allergic patients. Some CLV‐ADs induce the expression of activation, maturation, and migration markers on moDCs from allergic patients. Pre‐stimulated moDCs with some CLV‐ADs induces CD4+Th2 cell proliferation. The combination of the results from different CLV‐AD analogues increases LTT sensitivity to 65%.Abbreviations: ADs, antigenic determinants; CCR7, C‐C chemokine receptor type 7; CLV, clavulanic acid; LTT, lymphocyte transformation test; moDCs, monocyte‐derived dendritic cells
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影响因子：
12.4
作者：
Fernandez-Santamaria, Ruben;Palomares, Francisca;Fernandez, Tahia D.
通讯作者：
Fernandez, Tahia D.
影响因子：
12.4
作者：
Demoly, P.;Adkinson, N. F.;Thong, B. Y. -H.
通讯作者：
Thong, B. Y. -H.
影响因子：
12.4
作者：
Jose Torres, Maria;Celik, Gulfem Elif;Romano, Antonino
通讯作者：
Romano, Antonino
影响因子：
12.4
作者：
Cahen, YD;Wuthrich, B
通讯作者：
Wuthrich, B
影响因子：
12.4
作者：
Fernandez, T. D.;Torres, M. J.;Blanca, M.
通讯作者：
Blanca, M.