title: Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients.
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.
  
  
  CONCLUSIONS
  MGL_1304 is a major allergen in human sweat and could cause type I allergy in patients with AD.
authors.affiliation: 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.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hiragun
authors.affiliation: Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Hiragun
authors.affiliation: 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.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kan
authors.affiliation: Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Mihara
authors.affiliation: Department of Dermatology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yanase
authors.affiliation: Department of Dermatology, Clinical Research Unit Cutaneous Inflammation, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Bartels
authors.affiliation: Department of Dermatology, Clinical Research Unit Cutaneous Inflammation, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Jens-M
authors.initials: JM
authors.lastname: Schröder
authors.affiliation: 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.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hide
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D001491:Basophils / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology; D008290:Malassezia / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013542:Sweat / Q000276:immunology*; D055815:Young Adult
chemical_list: D000485:Allergens; D005656:Fungal Proteins; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E
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