Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement.
(2018) Nat Commun 9: 1421-1421
Authors: Orengo, J.M., Radin, A.R., Kamat, V., Badithe, A., Ben, L.H., Bennett, B.L., Zhong, S., Birchard, D., Limnander, A., Rafique, A., Bautista, J., Kostic, A., Newell, D., Duan, X., Franklin, M.C., Olson, W., Huang, T., Gandhi, N.A., Lipsich, L., Stahl, N., Papadopoulos, N.J., Murphy, A.J., Yancopoulos, G.D.
Abstract
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p?=?0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
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