Allergy and Immunology Section, Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, Room 509, Mall Road, Delhi, 110007, India.
J Clin Immunol. 2010 May;30(3):426-34. doi: 10.1007/s10875-009-9362-0. Epub 2010 Jan 14.
Purified allergens with reduced IgE reactivity are required to improve the safety and efficacy of allergen-specific immunotherapy (IT).
The present study investigates the efficacy of purified cockroach allergen immunotherapy with proteolytically active and inactive Per a 10 in allergic mouse model.
Balb/c mice were sensitized intraperitoneally with cockroach extract (CE) and purified allergen Per a 10 in separate groups. Mice were treated subcutaneously with phosphate-buffered saline (PBS), CE, active and inactive Per a 10 and challenged intranasally. Antigen specific IgE, IgG1 and IgG2a in serum and cytokines IL-4, IL-13, IFN-gamma, IL-10, TGF-beta in bronchoalveolar lavage (BAL) fluid and spleen culture supernatant (CS) were estimated by enzyme-linked immunosorbent assay. Lung histology was analyzed by hematoxylin and eosin staining.
IT with Per a 10 demonstrated significant reduction in IgE levels in serum, IL-4 levels in BAL fluid, CS, and eosinophilic infiltration in lungs than PBS-treated mice. This was associated with significantly increased IL-10 secretion in BAL fluid and CS. IT with Per a 10 effectively suppressed T-helper type 2 (Th2) response in mice sensitized with Per a 10 than CE group. Further, IT with inactive Per a 10 showed maximum reduction in systemic and airway inflammation and induced maximum IL-10 release in BAL fluid and CS than other antigens.
IT with Per a 10 effectively suppressed Th2 response and lung inflammation in Per a 10- or CE-sensitized mice. The beneficial effects of IT with inactive Per a 10 are more pronounced than active Per a 10.
为了提高变应原特异性免疫治疗（AIT）的安全性和疗效，需要使用 IgE 反应性降低的纯化过敏原。
本研究旨在探讨具有蛋白水解活性和无活性的 Per a 10 的纯化蟑螂过敏原免疫治疗在变应性小鼠模型中的疗效。
将 Balb/c 小鼠分别用蟑螂提取物（CE）和纯化过敏原 Per a 10 经腹腔致敏。用磷酸盐缓冲盐水（PBS）、CE、活性和无活性的 Per a 10 对小鼠进行皮下处理，并进行鼻腔内攻击。通过酶联免疫吸附试验测定血清中抗原特异性 IgE、IgG1 和 IgG2a 以及支气管肺泡灌洗液（BAL）和脾培养上清液（CS）中的细胞因子 IL-4、IL-13、IFN-γ、IL-10 和 TGF-β。通过苏木精和伊红染色分析肺组织学。
与 PBS 处理的小鼠相比，Per a 10 的 IT 显著降低了血清中的 IgE 水平、BAL 液中的 IL-4 水平、CS 中的 IL-4 水平以及肺部嗜酸性粒细胞浸润。这与 BAL 液和 CS 中 IL-10 分泌的显著增加有关。与 CE 组相比，Per a 10 的 IT 有效地抑制了 Per a 10 致敏小鼠的辅助性 T 细胞 2（Th2）反应。此外，与其他抗原相比，无活性 Per a 10 的 IT 显示出最大程度地降低了全身和气道炎症，并在 BAL 液和 CS 中诱导了最大的 IL-10 释放。
Per a 10 的 IT 有效地抑制了 Per a 10 或 CE 致敏小鼠的 Th2 反应和肺部炎症。无活性 Per a 10 的 IT 的有益效果比活性 Per a 10 更明显。
