TACI-Ig prevents the development of airway hyperresponsiveness in a murine model of asthma
TACI-Ig prevents the development of airway hyperresponsiveness in a murine model of asthma
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DOI：
10.1111/j.1365-2222.2008.03099.x
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发表时间：
2008-12-01
影响因子：
6.1
通讯作者：
Dillon, S. R.
中科院分区：
文献类型：
--
作者：
Bilsborough, J.;Chadwick, E.;Dillon, S. R.
血清IgE水平升高与哮喘患病率和疾病严重程度增加相关。使用抗IgE单克隆抗体消除IgE在治疗中度至重度和重度持续性过敏性哮喘中取得了成功。为了测试与IgE消除相比，B细胞靶向治疗是否是小鼠模型中气道高反应性（AHR）的更有效治疗。我们递送可溶性mTACI-Ig，一种B细胞存活因子BLyS受体（B淋巴细胞刺激因子）和APRIL（一种促增殖诱导配体），mTACI-Ig治疗降低了血液中循环成熟B细胞水平，而抗IgE治疗对B细胞计数没有影响。mTACI-Ig和抗IgE抗体均降低血清中总IgE和过敏原特异性IgE水平。肺组织病理学分析显示，两个治疗组的疾病严重程度评分均降低，但mTACI-Ig治疗组的结果更为明显。mTACI-Ig治疗后，支气管肺泡灌洗（BAL）中的中性粒细胞和嗜酸性粒细胞数量显著减少，但抗IgE给药后没有减少。BLyS和APRIL阻断还分别导致总肺匀浆和BAL液中IL-4和eotaxin mRNA以及IL-4和KC蛋白水平的显著降低。最后，mTACI-Ig治疗比抗IgE治疗更有效地减少AHR吸入抗原。我们的数据表明，在AHR的小鼠模型中，mTACI-Ig的递送比抗IgE mAb更有效。Chadwick，S.穆德里角是的，W。R.小亨德森，K.瓦吉湖Hebb，J. Shin，M. Rixon，J. A. Gross和S. R.狄龙，临床和实验过敏，2008（38）1959-1968。
Increased levels of serum IgE are associated with greater asthma prevalence and disease severity. IgE depletion using an anti-IgE monoclonal antibody has met with success in the treatment of moderate-to-severe and severe persistent allergic asthma.To test whether B cell-targeted therapy is a more effective treatment for airway hyperresponsiveness (AHR) in a murine model compared with IgE-depletion.We delivered soluble mTACI-Ig, a receptor for the B cell survival factors BLyS (B Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), or anti-IgE to allergen-sensitized mice before airway challenge with allergen.mTACI-Ig treatment reduced circulating mature B cell levels in the blood, while anti-IgE treatment had no effect on B cell counts. Both mTACI-Ig and anti-IgE decreased the levels of total and allergen-specific IgE in the serum. Histopathologic analysis of lungs showed a reduction in disease severity scores for both treatment groups, but results were more pronounced in mTACI-Ig-treated mice. Neutrophil and eosinophil numbers in the bronchoalveolar lavage (BAL) were significantly reduced following mTACI-Ig treatment, but not after anti-IgE delivery. BLyS and APRIL blockade also resulted in a significant decrease in IL-4 and eotaxin mRNA and IL-4 and KC protein levels in total lung homogenates and BAL fluid, respectively. Finally, mTACI-Ig treatment was more effective than anti-IgE treatment in reducing AHR to inhaled antigen.Our data demonstrate that delivery of mTACI-Ig is a more effective treatment than anti-IgE mAb in a murine model of AHR.Cite this as: J. Bilsborough, E. Chadwick, S. Mudri, X. Ye, W. R. Henderson Jr., K. Waggie, L. Hebb, J. Shin, M. Rixon, J. A. Gross and S. R. Dillon, Clinical and Experimental Allergy, 2008 (38) 1959-1968.