title: IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis.
abstract: 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 .
authors.affiliation: Swiss Institute of Allergy and Asthma Research, Davos, Switherland. peter.schmid@usz.ch
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.forename: Sabine
authors.initials: S
authors.lastname: Flückiger
authors.forename: Rainer
authors.initials: R
authors.lastname: Disch
authors.forename: Axel
authors.initials: A
authors.lastname: Trautmann
authors.forename: Brunello
authors.initials: B
authors.lastname: Wüthrich
authors.forename: Kurt
authors.initials: K
authors.lastname: Blaser
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
mesh_terms: 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
chemical_list: D000485:Allergens; D005656:Fungal Proteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D013482:Superoxide Dismutase