Nature

Malassezia yeasts, formally known as Pityrosporum orbiculare/ovale, are yeast-like unicellular fungi that form part of the normal skin flora in man and many animal species (1, 2). With the exception of Malassezia pachydermatitis, all Malassezia species are lipid dependent (3), which explains a predilection for seborrheic skin sites such as the head and neck (4). The species most commonly found on human skin are M. sympodialis, M. globosa and M. restricta (1, 4).

Malassezia yeasts form part of the healthy dermal microbiome and comprise 1–22 % of the phylogenetic composition of the skin microflora (4), which is dependent on the area of the body (5). Malassezia spp. are the main eukaryotic microbial flora normally found on the skin (4).

Malassezia spp. have been implicated in the pathogenesis of a diverse range of dermatological diseases, including pityriasis versicolor, folliculitis, seborrheic dermatitis, atopic dermatitis (AD) and psoriasis (6). An etiological role of Malassezia spp. in respiratory allergic disease, such as allergic rhinitis and asthma has also been proposed (7). However, other authors have suggested the pathophysiology of Malassezia in atopic disease is limited to allergic skin disease only (1, 2). 

Taxonomy

Allergenic molecules

Table based on data from Allergome.org (12)

Almost twenty allergens specific to Malassezia spp. are recognized by the WHO/IUIS Allergen Nomenclature Sub-committee. The best understood Malassezia spp. allergens are those described for M. sympodialis, (Mala s 5, 6, 10 and 14) which have sequence similarity to human proteins. Mala 1 and 7 have not similarity with any known proteins and their function remains undetermined. Mala s 11 has high sequence homology to the human mitochondrial enzyme manganese superoxide dismutase, as well as the homologous Aspergillus fumigatus enzyme (2).

A central European study found that a high proportion of patients with AD (24%) had elevated specific IgE for Mala s 1 (7). Furthermore, the same study described how sensitization of Mala s 11, along with Mala s 6, a cyclophilin, was associated with moderate-to-severe manifestations of disease. Mala s 6 sensitization was also associated with severe allergic rhinitis (7). Another study found strong correlation between positive skin prick test (SPT) and atopy patch test (APT) to recombinant Mala s 1, 5, 6 and 9 in patients with atopic eczema, with a reduced reaction observed for Mala s 7 (9).

A recent study using recombinant Mal f 1 on THP-1 derived dendritic cells has revealed a novel activation pathway, with significant elevation of TNF-α, Il-6 and Il-10 significantly elevated with no change in IL-12 levels (6). This indicates Mal f 1 triggers a TH22/TH17 pathway separate from the classic IgE-dependent Th2 pathway and could give an explanation why treatment targeting the Th2 pathway has reduced efficacy.

MGL_1304 is major allergen in human sweat and is secreted by M. globosa. One study showed MGL­_1304 triggered the highest histamine release activity from basophils of patients with allergic dermatitis and cholinergic urticaria who were challenged with Malassezia spp., antigens (11). In a further study, supMGL_1304 was strongly associated with eczema and total IgE, but not with sensitization to common airborne/inhalant allergens. The authors suggested that this supports hypothesis that a defective skin barrier enhances antigen uptake and sensitization (10).

Cross-reactivity

Malassezia specific allergens contain proteins with high sequence similarity to proteins from non-Malassezia genera (1). This is consistent with the general observation that the majority of fungal allergens have extensive cross-reactivity with fungi that are taxonomically unrelated (7). Consequently, Mala f 2 and 3 (peroxisomal membrane protein, or PMP), Mala s 6 (cyclophiline), Mala s 10 (Heat Shock Protein 70), Mala s 11 (MnSOD) and Mala s 13 (thioredoxin) all have the potential for cross-reactivity (1). The latter also has similarity with human proteins (7).