IgE-mediated and T cell–mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis

Cross-Reactivity and 1.4-Å Crystal Structure ofMalassezia sympodialisThioredoxin (Mala s 13), a Member of a New Pan-Allergen Family

“…As shown by comparison of the Mala s 13 and human Trx structures, the conserved areas forming patches able to accommodate putative cross-reactive B cell epitopes are quite limited. The most exciting aspect of the cross-reactivity between environmental allergens and self-Ags demonstrated here for Trx and elsewhere for other homologous molecular structures (9 -12, 20, 43) consists in their ability to influence the pathogenesis of severe atopic diseases (23). The availability of the crystal structures of allergen/self-Ag pairs provides structural information for the modification of the cross-reactive areas by site-directed mutagenesis.…”

“…Routine skin-prick tests (SPT) and atopy patch tests (APT) were performed with an in-house M. sympodialis (ATCC strain 42132) extract prepared as described previously (22). SPT and APT with Mala s 13 and human Trx were performed as described elsewhere (23). The study protocol was conducted according to a clinical protocol approved by the ethical committee of the University of Zurich, and all participants gave written informed consent after a full explanation of the procedure given individually before testing.…”

“…The clinical relevance of the cross-reactivity between Mala s 13 and human Trx was assessed by SPT and APT as described previously (23). Five patients with and five without allergen-specific IgE to Mala s 13 sensitized to M. sympodialis and five healthy controls were tested.…”

Overview of Aspergillus Allergens

“…Basically cross-reactivity can be traced back to conserved proteins sharing common B and T cell epitopes as shown for many allergen structures [33]. Amongst these MnSOD (Asp f 6) [57,58], P 2 acidic ribosomal protein (Asp f 8) [59], cyclophilins (Asp f 11 and Asp f 27) [30,60,61] and thioredoxins (Asp f 28 and Asp f 29) [29] have been shown to belong to families of cross-reactive pan-allergens. Per definition pan-allergens share a high degree of sequence identity at primary structure level, thus belonging to protein families showing similar structural folding [33,62].…”

“…The best investigated structures at this level are human MnSOD [57,58], cyclophilin [30,61] and thioredoxin [29], which were shown to bind to serum IgE from A. fumigatus sensitised patients in vitro, to elicit specific skin test reactions in vivo, and to be potentially involved in the pathogenesis of ABPA and atopic eczema [18,63]. Although the role played by IgE-mediated autoreactivity to self-antigens remains controversial, the fact that the application of human MnSOD in patch test on healthy skin areas of atopic eczema patients sensitised to fungal MnSOD is sufficient to induce an eczematous reaction [57,63] strongly indicates that autoreactivity could contribute to the exacerbation of the symptoms in the absence of external exposure to environmental allergens. For self-antigens showing a high degree of sequence identity/homology to environmental allergens, these reactions can be clearly explained by cross-reactive IgE antibodies primarily raised against external allergens.…”