IgE-mediated and T cell–mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis Peter Schmid-Grendelmeier, MD, Sabine Flückiger,

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Presentation transcript:

IgE-mediated and T cell–mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis Peter Schmid-Grendelmeier, MD, Sabine Flückiger, PhD, Rainer Disch, MD, Axel Trautmann, MD, Brunello Wüthrich, MD, Kurt Blaser, PhD, Annika Scheynius, MD, Reto Crameri, PhD Journal of Allergy and Clinical Immunology Volume 115, Issue 5, Pages 1068-1075 (May 2005) DOI: 10.1016/j.jaci.2005.01.065 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 A, The relationship between disease activity expressed by SCORAD and specific IgE against MnSOD in the subgroup sensitized against hMnSOD. B, Values of specific IgE against M sympodialis analyzed by ImmunoCAP are compared with specific IgE against hMnSOD measured by ELISA. C, The inhibition of detectable IgE levels against M sympodialis by fungal MnSOD (Asp f 6) and human MnSOD is shown, pointing out the cross-reactivity between these proteins and M sympodialis extract. Journal of Allergy and Clinical Immunology 2005 115, 1068-1075DOI: (10.1016/j.jaci.2005.01.065) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 PBMC proliferation after 6 days of exposure with optimal concentrations of the recombinant Asp f 6, hMnSO, and fungal extracts of A fumigatus and M sympodialis in 3 patients with AD, showing reactivity against MnSOD and M sympodialis in SPT, specific IgE, and APT in comparison with 3 patients with AD not sensitized against these allergens. Journal of Allergy and Clinical Immunology 2005 115, 1068-1075DOI: (10.1016/j.jaci.2005.01.065) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Atopy patch test reactivity after 48-hour application of the various fungal allergens and hMnSOD. The results clearly demonstrate an eczematous reaction to M sympodialis and hMnSOD in a patient with AD accordingly sensitized. The applied substances are (1) petrolatum, (2) rAsp f 6, (3) A fumigatus extract, (4) M sympodialis extract, (5) recombinant human MnSOD, and (6) saline. Journal of Allergy and Clinical Immunology 2005 115, 1068-1075DOI: (10.1016/j.jaci.2005.01.065) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Manganese superoxide dismutase staining in skin. By immunhistochemistry, the stage and disease-dependent expression of MnSOD in various human skin tissue samples are demonstrated. There is a mild expression of MnSOD in healthy skin (B) that rapidly increases in mild (C) and even more in severe AD (D). Application of topical corticosteroids (CS) in AD leads to decreased expression of MnSOD after 7 days (E, before; F, after). Interestingly, upregulation can also be induced by application of rhMnSOD in APT detectable after only 48 hours (G). The expression of hMnSOD is relatively low in ABPA (H) and other inflammatory skin diseases (I-L) except cutaneous T-cell lymphoma (CTCL) (L), pointing out the dependance of MnSOD production on inflammatory lymphatic cells. Journal of Allergy and Clinical Immunology 2005 115, 1068-1075DOI: (10.1016/j.jaci.2005.01.065) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions