Atopic dermatitis patients react differently to fungal proteins found in sweat

By Liz Meszaros, MDLinx
Published March 7, 2018

Key Takeaways

Patients with atopic dermatitis (AD) may have different hypersensitivities to the homologous proteins of MGL_1304, a fungal protein secreted by Malassezia globosa that is present in human sweat, according to results published in Allergology International.

MGL_1304 was recently discovered to be a major histamine-releasing antigen in human sweat.1 In patients with AD, recombinant MGL_1304 induces basophil histamine release. This is relevant because AD is exacerbated by sweating, and the skin of most AD patients is colonized with Malassezia fungi. A previous study showed that levels of MGL_1304-specific IgE correlated with AD severity.2

Malassezia is a fungi related to pityriasis versicolor, Malassezia folliculitis, seborrheic dermatitis, and AD.3 The 3 species (of 14) predominantly found on human skin in Japanese people are M. globosa, M. restricta, and M. sympodialis.4 The prevalence of M. globosa and M. restricta varies according to AD severity.5

Takuma Kohsaka, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, and colleagues conducted a study in which they cloned MGL_1304 in M. restricta and M. sympodialis, and assessed its allergenic potential in patients with AD.

Researchers included 64 AD patients (mean age: 28.2 years; 34 males; mean serum IgE: 6775.7 UI/ml; mean serum thymus and activation-regulated chemokine: 2644.5 pg/ml). Subjects were divided into four subgroups according to disease severity, which ranged from mild (n=18), moderate (n=23), and severe (n=12) to most severe (n=11), according to the Japanese AD severity index guideline.

Kohsaka et al obtained cultures of M. globosa, M. sympodialis, and M. restricta and extracted genomic DNA. Total RNA extraction and cDNA generation were completed by reverse transcriptase. They used western blot/dot blot analysis and histamine release tests (HRTs) to compare the allergenic potential of recombinant MGL_1304 and its counterparts Mala s 8 and Mala r 8, which are produced by M. sympodialis and M. restricta, respectively.

The researchers found that IgE binding was significantly higher against Mala s 8 than MGL_1304. Atopic dermatitis severity and IgE binding to MGL_1304, Mala s 8, and Mala r 8 had a weak but significant correlation, with the highest correlation seen with MGL_1304.

When Kohsaka and fellow researchers conducted HRT with basophils obtained from AD patients, they found significantly higher levels of histamine release against MGL_1304 and Mala r 8, compared with those with Mala s 8. Histamine release against the crude lysate of M. globosa was significantly higher than that achieved against M. sympodialis. Researchers observed no differences in histamine release against M. restricta and M. sympodialis.

Dot blot testing showed higher serum IgE binding to Mala s 8 compared with MGL_1304.

“In conclusion, patients with AD showed heterogeneous hypersensitivity against MGL_1304 and its homologs. MGL_1304, and Mala r 8 showed higher histamine release activities for basophils of patients with AD than Mala s 8,” the authors concluded. “The measurement of the other MGL_1304 homologs in human sweat, using assays specific for each homolog is warranted to reveal the causative mechanism of sweat allergy and adequate target for treatments to be developed.”


  1. Hiragun T, Ishii K, Hiragun M, et al. Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients. J Allergy Clin Immunol. 2013;132:608-615.e4.
  2. Hiragun M, Hiragun T, Ishii K, et al. Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and cholinergic urticaria. Allergol Int. 2014;63:83-93.
  3. Harada K, Saito M, Sugita T, Tsuboi R. Malassezia species and their associated skin diseases. J Dermatol. 2015;42:250-257.
  4. Sugita T, Suto H, Unno T, et al. Molecular analysis of Malassezia microflora on the skin of atopic dermatitis patients and healthy subjects. J Clin Microbiol. 2001;39:3486-3490.
  5. Kaga M, Sugita T, Nishikawa A, et al. Molecular analysis of the cutaneous Malassezia microbiota from the skin of patients with atopic dermatitis of different severities. Mycoses. 2011;54:e24-28.

This work was supported in part by JSPS KAKENHI Grant Number JP15K09767, and carried out in part at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University.

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