Induction of Epidermolysis Bullosa Acquisita in Mice by Passive Transfer of Autoantibodies from Patients David T. Woodley, Ramin Ram, Arvin Doostan,

Slides:

Advertisements

Similar presentations

Date of download: 7/8/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Congenital Epidermolysis Bullosa Acquisita: Vertical.

Advertisements

Volume 15, Issue 3, Pages (March 2007)

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters Artem Vorobyev, Hideyuki Ujiie, Andreas Recke,

Targeted Disruption of the Lama3 Gene in Adult Mice Is Sufficient to Induce Skin Inflammation and Fibrosis Monika Pesch, Sabrina König, Monique Aumailley

Donna A. Culton, Suzanne K. McCray, Moonhee Park, James C

Autoantibodies in Scurfy Mice and IPEX Patients Recognize Keratin 14

Journal of Allergy and Clinical Immunology

Intravenously Administered Recombinant Human Type VII Collagen Derived from Chinese Hamster Ovary Cells Reverses the Disease Phenotype in Recessive Dystrophic.

IL-21 Reduces Immediate Hypersensitivity Reactions in Mouse Skin by Suppressing Mast Cell Activation or IgE Production Risa Tamagawa-Mineoka, Tsunao.

Kevin P. White, MD, Daniel C. Zedek, MD, Wain L. White, MD, Eric L

Possible Involvement of Basement Membrane Damage in Skin Photoaging

Induction of Autoimmunity in a Bleomycin-Induced Murine Model of Experimental Systemic Sclerosis: An Important Role for CD4+ T Cells Hideaki Ishikawa,

The Autoantigen in Anti-p200 Pemphigoid Is Synthesized by Keratinocytes and Fibroblasts and Is Distinct from Nidogen-2 Silke C. Hofmann, Ursula Voith,

Bullous Pemphigoid: Using Animal Models to Study the Immunopathology

Deletion of the Major Bullous Pemphigoid Epitope Region of Collagen XVII Induces Blistering, Autoimmunization, and Itching in Mice Tiina Hurskainen,

Epidermolysis Bullosa Acquisita Develops in Dominant Dystrophic Epidermolysis Bullosa Ryota Hayashi, Ken Natsuga, Mika Watanabe, Hiroaki Iwata, Satoru.

Expression of Type XVI Collagen in Human Skin Fibroblasts: Enhanced Expression in Fibrotic Skin Diseases Atsushi Akagi, Shingo Tajima, Yutaka Nagai

IgG Binds to Desmoglein 3 in Desmosomes and Causes a Desmosomal Split Without Keratin Retraction in a Pemphigus Mouse Model Atsushi Shimizu, Akira Ishiko,

Basement Membrane Zone Remodeling During Appendageal Development in Human Fetal Skin. The Absence of Type VII Collagen is Associated with Gelatinase-A.

Heme-Scavenging Role of α1-Microglobulin in Chronic Ulcers

Refractory oral ulcers with multiple immunoglobulin G/immunoglobulin A autoantibodies without skin lesions Teruki Dainichi, MD, Bungo Ohyama, MD, Norito.

Effects of Intravenous Immunoglobulins on Mice with Experimental Epidermolysis Bullosa Acquisita Misa Hirose, Benjamin Tiburzy, Norito Ishii, Elena Pipi,

Topically Applied Hsp90 Blocker 17AAG Inhibits Autoantibody-Mediated Blister-Inducing Cutaneous Inflammation Stefan Tukaj, Katja Bieber, Konrad Kleszczyński,

Enhanced Cutaneous Inflammatory Reactions to Aspergillus fumigatus in a Murine Model of Chronic Granulomatous Disease Jeffrey E. Petersen Journal of.

Xiang Ding, Luis A. Diaz, Janet A. Fairley, George J. Giudice, Zhi Liu

Assembly of Epithelial Cell Fibrillins

Isolation of Pathogenic Monoclonal Anti-Desmoglein 1 Human Antibodies by Phage Display of Pemphigus Foliaceus Autoantibodies Ken Ishii, Chenyan Lin,

Toshiyuki Yamamoto, Kiyoshi Nishioka

Inherited Dystrophic Epidermolysis Bullosa in Inbred Dogs: A Spontaneous Animal Model for Somatic Gene Therapy Xavier Palazzi, Thierry Marchal, Luc Chabanne,

Aberrant Mineralization of Connective Tissues in a Mouse Model of Pseudoxanthoma Elasticum: Systemic and Local Regulatory Factors Qiujie Jiang, Qiaoli.

Evidence that Anti-Type VII Collagen Antibodies Are Pathogenic and Responsible for the Clinical, Histological, and Immunological Features of Epidermolysis.

Function Blocking Autoantibodies Against Matrix Metalloproteinase-1 in Patients with Systemic Sclerosis Shinichi Sato, Ikuko Hayakawa, Minoru Hasegawa,

Sustained Activation of Fibroblast Transforming Growth Factor-β/Smad Signaling in a Murine Model of Scleroderma Shinsuke Takagawa, Gabriella Lakos, Yasuji.

Collagen VII Half-Life at the Dermal-Epidermal Junction Zone: Implications for Mechanisms and Therapy of Genodermatoses Tobias Kühl, Markus Mezger, Ingrid.

Epitope-Dependent Pathogenicity of Antibodies Targeting a Major Bullous Pemphigoid Autoantigen Collagen XVII/BP180 Mayumi Wada, Wataru Nishie, Hideyuki.

Normal and Gene-Corrected Dystrophic Epidermolysis Bullosa Fibroblasts Alone Can Produce Type VII Collagen at the Basement Membrane Zone David T. Woodley,

Expression of T-Cadherin in Basal Keratinocytes of Skin

Interleukin-18 and the Costimulatory Molecule B7-1 Have a Synergistic Anti-Tumor Effect on Murine Melanoma; Implication of Combined Immunotherapy for.

Deletion of the Cytoplasmatic Domain of BP180/Collagen XVII Causes a Phenotype with Predominant Features of Epidermolysis Bullosa Simplex Marcel Huber,

Lack of Nidogen-1 and -2 Prevents Basement Membrane Assembly in Skin-Organotypic Coculture Roswitha Nischt, Cathrine Schmidt, Nicolae Mirancea, Anke.

Autoantibodies to Bullous Pemphigoid Antigen 180 Induce Dermal–Epidermal Separation in Cryosections of Human Skin Cassian Sitaru, Enno Schmidt, Steffen.

Increased Severity of Bleomycin-Induced Skin Fibrosis in Mice with Leukocyte-Specific Protein 1 Deficiency JianFei Wang, Haiyan Jiao, Tara L. Stewart,

Observations of Skin Grafts Derived from Keratinocytes Expressing Selectively Engineered Mutant Laminin-332 Molecules Noriyasu Sakai, Elizabeth A. Waterman,

Volume 102, Issue 5, Pages (September 2000)

SPARC-Null Mice Display Abnormalities in the Dermis Characterized by Decreased Collagen Fibril Diameter and Reduced Tensile Strength Amy D. Bradshaw,

Cloning of Hamster Type XVII Collagen cDNA, and Pathogenesis of Anti-Type XVII Collagen Antibody and Complement in Hamster Bullous Pemphigoid Katsushi.

A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice

Erythema Multiforme Associated Human Autoantibodies Against Desmoplakin I and II: Biochemical Characterization and Passive Transfer Studies Into Newborn.

A New Mouse Model of Junctional Epidermolysis Bullosa: The LAMB3 628G>A Knockin Mouse Johanna Hammersen, Jin Hou, Stephanie Wünsche, Sven Brenner, Thomas.

In Vivo Ultrastructural Localization of the Desmoglein 3 Adhesive Interface to the Desmosome Mid-Line Atsushi Shimizu, Akira Ishiko, Takayuki Ota, Hitoshi.

IgE Basement Membrane Zone Antibodies Induce Eosinophil Infiltration and Histological Blisters in Engrafted Human Skin on SCID Mice John J. Zone, Ted.

Apolipoprotein E is Present in Primary Localized Cutaneous Amyloidosis

IgG Autoantibodies from Bullous Pemphigoid (BP) Patients Bind Antigenic Sites on Both the Extracellular and the Intracellular Domains of the BP Antigen.

TAK1 Is Required for Dermal Wound Healing and Homeostasis

Expression of FcRn, the MHC Class I-Related Receptor for IgG, in Human Keratinocytes Karla Cauza, Gabriele Hinterhuber, Ruth Dingelmaier-Hovorka, Karin.

Pathogenicity and Epitope Characteristics of Anti-Desmoglein-1 from Pemphigus Foliaceus Patients Expressing Only IgG1 Autoantibodies Mary K. Hacker-foegen,

The Thomsen-Friedenreich Antigen-Binding Lectin Jacalin Interacts with Desmoglein-1 and Abrogates the Pathogenicity of Pemphigus Foliaceus Autoantibodies.

Shigeru Kusuda, Cui Chang-Yi, Masae Takahashi, Tadashi Tezuka

The 97 kDa Linear IgA Bullous Dermatosis Antigen is not Expressed in a Patient with Generalized Atrophic Benign Epidermolysis Bullosa with a Novel Homozygous.

Autoantibody in Mucous Membrane Pemphigoid Binds to an Intracellular Epitope on Human β4 Integrin and Causes Basement Membrane Zone Separation in Oral.

Autoantibodies to BP180 Associated with Bullous Pemphigoid Release Interleukin-6 and Interleukin-8 from Cultured Human Keratinocytes Enno Schmidt, Stanislaus.

Severity and Phenotype of Bullous Pemphigoid Relate to Autoantibody Profile Against the NH2- and COOH-Terminal Regions of the BP180 Ectodomain Silke.

Flor Evangelista, David A. Dasher, Luis A. Diaz, Phillip S

A Subset of Pemphigus Foliaceus Patients Exhibits Pathogenic Autoantibodies Against Both Desmoglein-1 and Desmoglein-3 Luis A. Arteaga, Philip S. Prisayanh,

Marcel F. Jonkman, Prof. Dr, Hendri H

Staphylococcal Exfoliative Toxin B Specifically Cleaves Desmoglein 1

Errata Journal of Investigative Dermatology

Generation of Antibodies of Distinct Subclasses and Specificity Is Linked to H2s in an Active Mouse Model of Epidermolysis Bullosa Acquisita Ralf J.

Recombinant Soluble CD32 Suppresses Disease Progression in Experimental Epidermolysis Bullosa Acquisita Hiroaki Iwata, Elena Pipi, Nicole Möckel, Peter.

Matrix Metalloproteinase Inhibitor BB-3103 Unlike the Serine Proteinase Inhibitor Aprotinin Abrogates Epidermal Healing of Human Skin Wounds Ex Vivo1

Presentation transcript:

Induction of Epidermolysis Bullosa Acquisita in Mice by Passive Transfer of Autoantibodies from Patients David T. Woodley, Ramin Ram, Arvin Doostan, Pubali Bandyopadhyay, Yi Huang, Jennifer Remington, Yingping Hou, Douglas R. Keene, Zhi Liu, Mei Chen Journal of Investigative Dermatology Volume 126, Issue 6, Pages 1323-1330 (June 2006) DOI: 10.1038/sj.jid.5700254 Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Characterization of affinity-purified EBA antibodies. (a) The figure shows the specificity of affinity-purified EBA autoantibodies for the NC1 domain of type VII collagen. Purified recombinant NC1 as well as other extracellular matrix components (400ng/well) were separated on a 6% SDS-PAGE gel and transferred to nitrocellulose membranes. The transferred proteins were incubated with affinity-purified EBA antibodies at a dilution of 1:2,000 and horseradish peroxidase conjugated anti-human IgG (1:5,000) followed by ECL detection. Lanes 1, 2, 3, 4, 5, and 6 are NC1, type I collagen, type IV collagen, fibronectin, laminin-1, and laminin-5, respectively. The location of the 145kDa recombinant NC1 and molecular weight markers are indicated. (b–d) The figure shows immunolabeling of mouse and human skin with the affinity-purified EBA antibodies. Immunofluorescence staining was performed on (b) human skin, (c) mouse skin, and (d) salt-split human skin. The tissue was labeled with EBA antibodies diluted 1:1,000 and an FITC-conjugated goat anti human IgG. Note that the affinity-purified EBA antibody strongly labeled the BMZ of both mouse and human skin and the dermal floor of salt-split human skin. d, dermis; e, epidermis. Bars, 200μm. Journal of Investigative Dermatology 2006 126, 1323-1330DOI: (10.1038/sj.jid.5700254) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Clinical appearance of SKH1 mice injected with EBA antibodies. (a–f) Middle back of SKH1 mice were injected intradermally with EBA antibodies at 50μg/g body weight once every day for 8 consecutive days. Four to six days after the injections were started, animals developed numerous blisters, erosions, and crusts forming from ruptured blisters (a, 4 × and b, 6 ×). Lesions were observed on the animals' paws (d) at 10 days and neck (c) at 6 weeks after the initial injections (8 ×). Nail loss was also observed in some mice (e and f). (g–i) Relation between the dose of EBA antibodies injected into mice and the extent of cutaneous lesions induced in the animals. The mice shown in panel g, panel h, and panel i received 50, 10, or 2.5μg IgG/g body weight, respectively, daily for 8 consecutive days. The arrows point to areas of blisters and erosions induced by EBA antibodies 8 days after the initial injections (8 ×). No lesions were observed in the animal in panel i. Journal of Investigative Dermatology 2006 126, 1323-1330DOI: (10.1038/sj.jid.5700254) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Histological and immunological examination of lesional skin of SKH1 mice injected with EBA antibodies. (a and b) Histological appearance of skin lesions induced by EBA autoantibodies. Hematoxylin and eosin staining of (a) lesional murine skin revealed separation of the epidermis (E) from the dermis (D). This histologic finding is similar to that seen in lesional skin of EBA patients. (b) No epidermal–dermal separation was seen in mice receiving equivalent amounts of normal human control IgG. (c) Immunofluorescence analysis of SKH1 mice skin injected with EBA antibodies. Cryosections of perilesional and lesional skin were labeled with FITC-conjugated goat anti-human IgG (α-H IgG), FITC-conjugated goat anti-mouse C3 (α-C3), and FITC-conjugated goat anti-mouse neutrophils (α-PMN), respectively. Note the linear deposits of human IgG and murine C3 at the BMZ of perilesional and lesional skin in mice injected with EBA antibodies. Please also note the scattered neutrophils in the dermis. In contrast, in mice receiving equivalent amounts of purified control normal human IgG (NHS), no deposits of human IgG or murine C3 were detected. d, dermis; e, epidermis. Original magnification, × 25. Journal of Investigative Dermatology 2006 126, 1323-1330DOI: (10.1038/sj.jid.5700254) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Immunolabeling of human skin with serum from mice injected with EBA antibodies. Sections of (a, c) normal human skin and (b) salt-split human skin were stained with mouse serum obtained from mice injected with either (a, b) EBA antibodies or (c) control human IgG at a dilution of 1:100. Note that circulating antibodies labeling the BMZ of human skin and the dermal floor of salt split human skin were found in the serum samples from mice injected with EBA antibodies, but not in those injected with normal human control IgG. d, dermis; e, epidermis. Journal of Investigative Dermatology 2006 126, 1323-1330DOI: (10.1038/sj.jid.5700254) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Immunoelectron microscopy of mice skin injected with EBA antibodies. (a) Perilesional and (b) lesional skin of mice injected with affinity-purified EBA autoantibodies were subjected to direct immunogold labeling with goat anti-human IgG conjugated with a 1nm gold particle. Note that the injected human IgG specifically deposited along the lamina densa of the BMZ, anchoring fibrils, and anchoring plaques. A split is also present in the sub-lamina densa region of the lesional skin. Arrows denote gold particle-labeled human IgG. D, dermis; E, epidermis; and HD, hemidesmosome. Bars, for (a) 200nm and for (b) 500nm. Journal of Investigative Dermatology 2006 126, 1323-1330DOI: (10.1038/sj.jid.5700254) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Clinical and immunological examination of SKH1 mice injected with the F(ab′)2 fragments generated from EBA antibodies. (a) Clinical appearance of skin injected with F(ab′)2 fragments at 40μg/g body weight once every day for 8 consecutive days showed no signs of skin blisters. (b–d) Immunofluorescence analysis of SKH1 mice skin injected with F(ab′)2 fragments of EBA antibodies. Cryosections of injected skin were labeled with FITC-conjugated (b) goat anti-human Fab, (c) goat anti-human Fc, and (d) goat anti-mouse C3, respectively. Note the strong binding of F(ab′)2 fragments to the BMZ, but the absence of Fc and murine C3 complement within the BMZ. Journal of Investigative Dermatology 2006 126, 1323-1330DOI: (10.1038/sj.jid.5700254) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions