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TACI‐Ig prevents the development of airway hyperresponsiveness in a murine model of asthma
Author(s) -
Bilsborough J.,
Chadwick E.,
Mudri S.,
Ye X.,
Henderson W. R.,
Waggie K.,
Hebb L.,
Shin J.,
Rixon M.,
Gross J. A.,
Dillon S. R.
Publication year - 2008
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2008.03099.x
Subject(s) - immunoglobulin e , immunology , medicine , eosinophil , asthma , bronchoalveolar lavage , allergen , immunotherapy , antibody , allergy , lung , immune system
Summary Background 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. Objective To test whether B cell‐targeted therapy is a more effective treatment for airway hyperresponsiveness (AHR) in a murine model compared with IgE‐depletion. Methods 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. Results 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. Conclusions Our data demonstrate that delivery of mTACI‐Ig is a more effective treatment than anti‐IgE mAb in a murine model of AHR.