[HTML][HTML] Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement

JM Orengo, AR Radin, V Kamat, A Badithe… - Nature …, 2018 - nature.com
JM Orengo, AR Radin, V Kamat, A Badithe, LH Ben, BL Bennett, S Zhong, D Birchard…
Nature communications, 2018nature.com
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 …
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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