Local inflammation exacerbates cutaneous manifestations in a murine autoimmune pemphigus model Sachiko Ono, MD, Gyohei Egawa, MD, PhD, Akihiko Kitoh,

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Presentation transcript:

Local inflammation exacerbates cutaneous manifestations in a murine autoimmune pemphigus model Sachiko Ono, MD, Gyohei Egawa, MD, PhD, Akihiko Kitoh, MD, PhD, Teruki Dainichi, MD, PhD, Atsushi Otsuka, MD, PhD, Saeko Nakajima, MD, PhD, Tetsuya Honda, MD, PhD, Kenji Kabashima, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 6, Pages 2026-2028.e5 (June 2017) DOI: 10.1016/j.jaci.2016.12.959 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Anti-Dsg3 antibody deposition in the untreated and PMA-painted skin. A, Time-lapse images and ΔFITC-MFI of epidermis in the PMA-painted (PMA) or untreated (UT) ear after FITC-labeled AK18 injection. B, Identification of IgG1 among keratinocytes. C, IgG1-MFI after 20 μg of AK18 or control IgG1 injection. D, ΔIgG1-MFI against AK18 injection doses. E and F, DIF after injection of AK18 (Fig 1, E), or serum from a healthy donor or a pemphigus patient (F). FITC, Fluorescein isothiocyanate. *P < .05. Journal of Allergy and Clinical Immunology 2017 139, 2026-2028.e5DOI: (10.1016/j.jaci.2016.12.959) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Anti-Dsg3 antibody deposition under various skin inflammatory conditions. A-C, IgG1-MFI of hapten-painted (Fig 2, A), tape-stripped (Fig 2, B), and UVB-irradiated ears (Fig 2, C) compared with that of untreated ears. D, A plot of ear swellings against IgG1-MFI in Fig 2, C. E and F, Hair loss (Fig 2, E) and AK23 deposition (Fig 2, F) limited to the PMA-painted area. G, IgG1-MFI of the ear after a histamine- or vehicle (Veh)-prick. Precise information is located in this article's Methods section in the Online Repository at www.jacionline.org. UT, Untreated; UVB, ultraviolet B. *P < .05. Journal of Allergy and Clinical Immunology 2017 139, 2026-2028.e5DOI: (10.1016/j.jaci.2016.12.959) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A flow cytometry–based analysis for detecting AK18 deposition in the murine epidermis. A, A schema of preparation of epidermal cell suspension. B, Identification of keratinocytes (a) and hematopoietic cells (b). C, Expression of Fcγ receptors among keratinocytes, compared with isotype-stained control. D, Identification of IgG1 and IgG1-MFI among keratinocytes after injection of PBS, 20 μg of AK18, or 20 μg of control IgG1, in PMA-painted or untreated ears. *P < .05. NS, Not significant; UT, untreated. Journal of Allergy and Clinical Immunology 2017 139, 2026-2028.e5DOI: (10.1016/j.jaci.2016.12.959) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Human anti-Dsg3 antibody deposition in the untreated and PMA-painted mouse skin. Immunohistochemical evaluation for antibody deposition after intravenous injection of various doses of serum from a patient with PV (PV2) whose anti-Dsg3 antibodies were of IgG4 subclass. UT, Untreated. Journal of Allergy and Clinical Immunology 2017 139, 2026-2028.e5DOI: (10.1016/j.jaci.2016.12.959) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Phenotype of a murine pemphigus model. Manifestation of hair loss after intravenous injection of AK23 or AK18. The injection dose is indicated above each mouse. Journal of Allergy and Clinical Immunology 2017 139, 2026-2028.e5DOI: (10.1016/j.jaci.2016.12.959) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 A conceptual drawing of kinetics of IgGs including anti-Dsg antibodies in the skin. A, No nonspecific IgGs deposition in the epidermis. B, Low epidermal anti-Dsg antibody deposition and unapparent skin manifestations with low serum antibody titers. C, Accumulation of epidermal anti-Dsg antibody deposition and induction of intraepidermal blistering with high serum antibody titers. D, Enhancement of epidermal anti-Dsg antibody deposition by local inflammation and induction of intraepidermal blistering with low serum antibody titers. Abs, Antibodies. Journal of Allergy and Clinical Immunology 2017 139, 2026-2028.e5DOI: (10.1016/j.jaci.2016.12.959) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions