IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis.
BACKGROUND
Autoreactivity of patients with atopic dermatitis (AD) to human proteins has been postulated as a decisive pathogenetic factor for AD.


OBJECTIVE
In this study, it was investigated whether the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of human and fungal origin might act as an autoallergen in atopic dermatitis.


METHODS
Patients with AD (n = 69; mean SCORAD [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as with inhalant allergies were investigated. The presence of specific IgE against recombinant MnSOD of fungal and human origin and the fungal extracts of Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC proliferation assays. Cross-reactivity between allergens was determined by CAP inhibition. The presence of MnSOD in human skin in various inflammatory skin conditions was investigated by immunohistochemistry.


RESULTS
Specific IgE antibodies against human MnSOD correlating with the disease activity were found in 29 out of 67 patients with AD. The human protein was able to induce in vitro T-cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin specimens. Cosensitization to structurally related and cross-reacting fungal MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients sensitized against human MnSOD.


CONCLUSIONS
Human MnSOD may play a role as an autoallergen in a subset of patients with AD, including nonatopic eczema. By molecular mimicry leading to cross-reactivity such sensitization might be induced primarily by exposure to environmental fungal MnSOD of M sympodialis .
Schmid-Grendelmeier
Peter
P
Swiss Institute of Allergy and Asthma Research, Davos, Switherland. peter.schmid@usz.ch
Flückiger
Sabine
S
Disch
Rainer
R
Trautmann
Axel
A
Wüthrich
Brunello
B
Blaser
Kurt
K
Scheynius
Annika
A
Crameri
Reto
R
D000328:Adult; D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000918:Antibody Specificity; D001232:Aspergillus fumigatus / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D002478:Cells, Cultured; D003429:Cross Reactions; D003876:Dermatitis, Atopic / Q000097:blood / Q000209:etiology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008290:Malassezia / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology; D012867:Skin / Q000378:metabolism; D012882:Skin Tests; D013482:Superoxide Dismutase / Q000009:adverse effects / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D005656:Fungal Proteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D013482:Superoxide Dismutase