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局部鼻内免疫疗法用桦树花粉-半乳甘露聚糖缀合物软膏在小鼠和人体中的应用。

Local nasal immunotherapy with birch pollen-galactomannan conjugate-containing ointment in mice and humans.

机构信息

Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Bio & Healthcare Business Division, Wako Filter Technology Co., Ltd., Ibaraki, Japan.

出版信息

Allergol Int. 2024 Apr;73(2):290-301. doi: 10.1016/j.alit.2023.10.007. Epub 2023 Nov 18.

Abstract

BACKGROUND

Allergen immunotherapy (AIT) is the only disease-modifying treatment for immunoglobulin (Ig) E-mediated allergy. Owing to the high prevalence and early onset of hay fever and pollen-food allergy syndrome (PFAS), a safer and simpler treatment method than conventional AIT is needed. To develop a local nasal immunotherapy using an ointment containing hypoallergenic pollen and assess its efficacy in mice and healthy humans.

METHODS

Hypoallergenicity was achieved by combining pollen and galactomannan through the Maillard reaction to create birch pollen-galactomannan conjugate (BP-GMC). The binding of galactomannan to Bet v 1 was confirmed using electrophoresis and Western blotting (WB). Binding of specific IgE antibodies to BP-GMC was verified using enzyme-linked immunosorbent assay (ELISA) and basophil activation test (BAT). The localization of BP-GMC absorption was confirmed using a BALB/c mouse model. BP-GMC mixed with white petrolatum was intranasally administered to 10 healthy individuals (active drugs, 8; placebo, 2) for 14 days.

RESULTS

In electrophoresis and WB, no 17-kDa band was observed. In ELISA and BAT, BP-GMC did not react to specific IgE but was bound to IgA and IgG. In the mouse model, BP-GMC was detected in nasopharyngeal-associated lymphoid tissues. In the active drug group, the salivary-specific IgA level significantly increased on day 15 (p = 0.0299), while the serum-specific IgG level significantly increased on day 85 (p = 0.0006).

CONCLUSIONS

The BP-GMC ointment rapidly produced antagonistic antibodies against IgE; it is safe and easy to use and might serve as a therapeutic antigen for hay fever and PFAS.

摘要

背景

变应原免疫疗法(AIT)是唯一可改变 IgE 介导过敏的疾病治疗方法。鉴于花粉热和花粉-食物过敏综合征(PFAS)的高发病率和发病早,需要一种比传统 AIT 更安全、更简单的治疗方法。本研究旨在开发一种使用含有低变应原花粉的软膏进行局部鼻内免疫疗法,并评估其在小鼠和健康人群中的疗效。

方法

通过美拉德反应将花粉和半乳甘露聚糖结合,制得桦树花粉-半乳甘露聚糖结合物(BP-GMC),从而实现花粉的低变应原性。电泳和 Western blot(WB)证实半乳甘露聚糖与 Bet v 1 的结合。酶联免疫吸附试验(ELISA)和嗜碱性粒细胞激活试验(BAT)验证特异性 IgE 抗体与 BP-GMC 的结合。使用 BALB/c 小鼠模型证实 BP-GMC 的吸收定位。将 BP-GMC 与白凡士林混合,经鼻内给药 14 天,共 10 名健康个体(活性药物 8 名,安慰剂 2 名)。

结果

电泳和 WB 中未观察到 17-kDa 条带。ELISA 和 BAT 中,BP-GMC 不与特异性 IgE 反应,但与 IgA 和 IgG 结合。在小鼠模型中,BP-GMC 可在鼻咽相关淋巴组织中检测到。在活性药物组中,唾液特异性 IgA 水平在第 15 天显著升高(p=0.0299),而血清特异性 IgG 水平在第 85 天显著升高(p=0.0006)。

结论

BP-GMC 软膏可快速产生针对 IgE 的拮抗性抗体;其使用安全且简便,可能成为花粉热和 PFAS 的治疗性抗原。

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