Fungal protein MGL-1304 in sweat is an allergen for atopic dermatitis patients

摘要

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 FcéRI 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.