Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients

Takaaki Hiragun; Kaori Ishii; Makiko Hiragun; Hidenori Suzuki; Takanobu Kan; Shoji Mihara; Yuhki Yanase; Joachim Bartels; Jens-M Schröder; Michihiro Hide

doi:10.1016/j.jaci.2013.03.047

Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients

J Allergy Clin Immunol. 2013 Sep;132(3):608-615.e4. doi: 10.1016/j.jaci.2013.03.047. Epub 2013 May 29.

Authors

Affiliations

¹ Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
² Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
³ Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Faculty of Human Science, Hiroshima Bunkyo Women's University, Hiroshima, Japan.
⁴ Department of Dermatology, Clinical Research Unit Cutaneous Inflammation, University Hospital Schleswig-Holstein, Kiel, Germany.
⁵ Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: ed1h-w1de-road@hiroshima-u.ac.jp.

PMID: 23726042
DOI: 10.1016/j.jaci.2013.03.047

Abstract

Background: Sweat is a major aggravating factor of atopic dermatitis (AD) and approximately 80% of patients with AD show type I hypersensitivity against sweat.

Objective: To identify and characterize an antigen in sweat that induces histamine release from basophils of patients with AD.

Methods: Basophil histamine-releasing activity in sweat was purified by a combination of chromatographies, and proteins were analyzed with mass spectrometry. Recombinant proteins of the sweat antigen were generated, and their biological characteristics were studied by immunoblots, histamine release tests, and neutralization assays.

Results: We identified a fungal protein, MGL_1304, derived from Malassezia globosa (M globosa) in the purified sweat antigen. Recombinant MGL_1304 induced histamine release from basophils of most of the patients with AD, in accordance with the semi-purified sweat antigen. Moreover, recombinant MGL_1304 abolished the binding of serum IgE of patients with AD to the semi-purified sweat antigen, or vice versa in immunoblot analysis, and attenuated the sensitization of RBL-48 mast cells expressing human FcɛRI by serum IgE. Studies of truncated mutants of MGL_1304 indicated that IgE of patients with AD recognized the conformational structure of MGL_1304 rather than short peptide sequences. Western blot analysis of the whole lysate, the culture supernatant of M globosa, and the semi-purified sweat antigen showed that MGL_1304 was produced as a minor immunological antigen of M globosa with posttranslational modification, cleaved, and secreted as a 17-kDa major histamine-releasing sweat antigen.

Conclusion: MGL_1304 is a major allergen in human sweat and could cause type I allergy in patients with AD.

Keywords: AD; AR; Allergic rhinitis; Atopic dermatitis; HRT; Histamine release test; Human manganese superoxide dismutase; IgE; Malassezia globosa; Sweat; TF; Trigger factor; atopic dermatitis; hMnSOD; histamine release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Allergens / immunology*
Basophils / drug effects
Basophils / immunology
Cell Line
Cells, Cultured
Dermatitis, Atopic / immunology*
Female
Fungal Proteins / genetics
Fungal Proteins / immunology*
Histamine Release / drug effects
Humans
Immunoglobulin E / blood
Interleukin-4 / immunology
Malassezia / immunology*
Male
Mast Cells / immunology
Recombinant Proteins / pharmacology
Sweat / immunology*
Young Adult

Substances

Allergens
Fungal Proteins
Recombinant Proteins
Interleukin-4
Immunoglobulin E