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A human monoclonal IgE antibody that binds to MGL_1304, a major allergen in human sweat, without activation of mast cells and basophils

Author:
Ishii, Kaori, Hiragun, Makiko, Hiragun, Takaaki, Kan, Takanobu, Kawaguchi, Tomoko, Yanase, Yuhki, Tanaka, Akio, Takahagi, Shunsuke, Hide, Michihiro
Source:
Biochemical and biophysical research communications 2015 v.468 pp. 99-104
ISSN:
0006-291X
Subject:
Malassezia, allergens, antibodies, antibody detection, atopic dermatitis, basophils, blood serum, detection limit, enzyme-linked immunosorbent assay, histamine, humans, immunoglobulin E, mast cells, neutralization, patients, sweat, urticaria
Abstract:
MGL_1304, a major allergen in human sweat for patients with atopic dermatitis and/or cholinergic urticaria, is secreted from Malassezia globosa on human skin. The amounts of MGL_1304 and IgE against MGL_1304 are evaluated by the histamine release test using basophils or mast cells sensitized with serum containing IgE against MGL_1304, and enzyme linked sorbent assay (ELISA) using MGL_1304 and anti-MGL_1304 antibodies. Here, we identified a human monoclonal IgE (ABS-IgE) that binds to the high affinity IgE receptor (FcεRI) and MGL_1304 with high affinity (KD = 1.99 nM) but does not release histamine from basophils and mast cells. An ELISA using ABS-IgE as a standard IgE revealed that the amount of IgE against MGL_1304 (1000 U/ml) in the standard sera of patients with AD, employed in our previous report, is 32 ng/ml. A sandwich ELISA using ABS-IgE as a detection antibody showed approximately 10 times lower detection limit for MGL_1304 than ELISA in which MGL_1304 is directly bound to an ELISA plate. Moreover, ABS-IgE prevented histamine release from mast cells and basophils by neutralizing MGL_1304 not only in a free form in solution, but also on FcεRI expressed on the cell surface without cell activation. ABS-IgE may be used both to quantify the amount of MGL_1304 and anti-MGL_1304 IgE, and possibly for the treatment of diseases caused/aggravated by type I allergy to MGL_1304.
Agid:
5332791