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Mark Yulis, Miguel Quiros, Roland Hilgarth, Charles A Parkos, Asma Nusrat
Desmosomal cadherins mediate intercellular adhesion and have also been shown to regulate homeostatic signaling in epithelial cells. We have previously reported that select pro-inflammatory cytokines induce Dsg2 ectodomain cleavage and shedding from intestinal epithelial cells (IECs). Dsg2 extracellular cleaved fragments (Dsg2 ECF) function to induce paracrine pro-proliferative signaling in epithelial cells. In this study, we show that exposure of IECs to pro-inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment (Dsg2 ICF)...
March 9, 2018: Cell Death & Disease
Luca Giannetti, Luigi Generali, Carlo Bertoldi
Involvement of the oral mucosa in patients affected by Pemphigus Vulgaris (PV), Paraneoplastic, IgA Pemphigus and in some cases of Iatrogenic Pemphigus is common, and precede skin lesions in the majority of cases. Intraepidermal bullae are caused by acantholysis, induced by IgG autoantibodies directed against the desmosomes and the domain of numerous keratinocytes self-antigens desmogleins (namely cadherins), thus supporting the autoimmune nature of the disease. Apoptosis may contribute to the acantholysis...
March 6, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Alexander K C Leung, Benjamin Barankin, Kin Fon Leong
BACKGROUND: Staphylococcal-scalded skin syndrome (SSSS), also known as Ritter disease, is a potentially life-threatening disorder and a pediatric emergency. Early diagnosis and treatment is imperative to reduce the morbidity and mortality of this condition. The purpose of this article is to familiarize physicians with the evaluation, diagnosis, and treatment of SSSS. DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "Staphylococcal scalded skin syndrome" and "Ritter disease"...
March 5, 2018: World Journal of Pediatrics: WJP
D Miyamoto, C W Maruta, C G Santi, P Zoroquiain, A B T Dias, J J Mansure, M N Burnier, V Aoki
BACKGROUND: Erythroderma is a severe manifestation of pemphigus foliaceus (PF), a blistering disease mediated by IgG autoantibodies against desmoglein-1. Increasing evidence supports the contribution of angiogenic mediators in the pathogenesis of erythroderma. OBJECTIVE: To evaluate the in situ expression of vascular endothelial growth factor (VEGF) and endoglin in PF patients with erythroderma. METHODS: Formalin-fixed paraffin-embedded skin samples obtained from patients with erythrodermic PF (n=19; 12 patients with endemic PF), non-erythrodermic PF (n=17), pemphigus vulgaris (PV; n=10), psoriasis (n=10), and healthy individuals (HI; n=10) were processed in an automated immunohistochemistry platform utilizing anti-VEGF and anti-endoglin as primary antibodies...
February 28, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Hedieh Saffari, John J Zone, Marjorie Allen, Kristin M Leiferman
BACKGROUND: Pemphigoid (herpes) gestationis (PG) is an uncommon, self-limited disease with other autoimmune associations; however, celiac disease (CD) is not recognized as one. METHODS: From 71 patients' sera submitted for herpes gestationis factor (HGF) testing over a 5-year period, 12 were consistent with PG demonstrating HGF and increased IgG BP180 antibody levels; these sera were tested for IgA and IgG endomysial antibodies (EMA), epithelial basement membrane zone and cell surface antibodies by indirect immunofluorescence, and for IgA and IgG tissue transglutaminase (transglutaminase 2 or TG2) antibodies, IgA epidermal transglutaminase (transglutaminase 3 or TG3) antibodies, IgG BP230, and IgG desmoglein 1 and desmoglein 3 antibodies by enzyme-linked immunosorbent assays (ELISAs)...
February 23, 2018: International Journal of Dermatology
Jimena Sanz-Bueno, Elena Gallo, Dolores Caro-Gutiérrez, Araceli Sánchez-Gilo, Marta Gutiérrez Pascual, Laura Rojas-Scheffer, Francisco Javier Vicente-Martín
El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy...
October 15, 2017: Dermatology Online Journal
T Baltazard, F Dhaille, S Duvert-Lehembre, C Lok, G Chaby
BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disorder characterized by linear IgA deposits along the dermoepidermal junction. Usually idiopathic, LABD can be drug-induced. OBJECTIVE: To report the atypical characteristics of a case of trimethoprim-sulfamethoxazole-induced LABD presenting as toxic epidermal necrolysis (TEN). METHODS: A 63-year-old woman treated with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii infection developed a generalized maculopapular rash with herpetiform lesions, rosette-like lesions, and tense bullae with Nikolsky sign...
August 15, 2017: Dermatology Online Journal
Volker Spindler, Jens Waschke
Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs) 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components...
2018: Frontiers in Immunology
Tomoko Sumitomo, Yasushi Mori, Yuumi Nakamura, Mariko Honda-Ogawa, Seitaro Nakagawa, Masaya Yamaguchi, Hiroyuki Matsue, Yutaka Terao, Masanobu Nakata, Shigetada Kawabata
Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. Dysfunction of desmosomes is associated with the pathogenesis of cutaneous diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. In an epicutaneous infection model, lesional skin infected with an speB deletion mutant were significantly smaller as compared to those caused by the wild-type strain...
2018: Frontiers in Cellular and Infection Microbiology
Marwah Adly Saleh
BACKGROUND: Rituximab (RTX) is an effective therapy for patients with pemphigus. However it does not prevent relapse. OBJECTIVES: To compare early relapsing patients (before 12 months) and late relapsing patients (after 24 months) following RTX therapy. METHODS: In this prospective study, 19 patients were enrolled (14 pemphigus vulgaris and 5 pemphigus foliaceus). The baseline disease score, autoantibodies, and percentage of CD20+ cells of pemphigus patients were measured...
January 30, 2018: Journal of the American Academy of Dermatology
Akemi Ishida-Yamamoto, Satomi Igawa, Mari Kishibe, Masaru Honma
Desmosomes provide the main intercellular adhesive properties between epidermal keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the loss of intercellular adhesion or acantholysis. When keratinocytes differentiate from granular cells into cornified cells, desmosomes are transformed into corneodesmosomes and can provide stronger intercellular adhesion. Degradation of corneodesmosomes is a tightly regulated process involving a number of proteases and their inhibitors...
January 19, 2018: Journal of Dermatology
Alexandra C Perks, Paula M Farthing, Ruth Murphy, Anne M Hegarty
Pemphigus is a chronic autoimmune condition that can affect multiple areas of the body. The two main subtypes of pemphigus are pemphigus vulgaris (PV) and pemphigus foliaceus (PF) which can rarely occur concurrently or even transition from one to the other. The process of transition may be explained by qualitative changes in desmoglein autoantibody profile. We present a rare case of concomitant PF and oral PV and explore the literature on transitions between pemphigus subtypes and whether this case could represent a transition from PF to PV...
January 16, 2018: Head and Neck Pathology
Nirk E Quispe Calla, Rodolfo D Vicetti Miguel, Melissa E Glick, Jesse J Kwiek, Janelle M Gabriel, Thomas L Cherpes
INTRODUCTION: HIV affects more women than any other life-threatening infectious agent, and most infections are sexually transmitted. HIV must breach the female genital tract mucosal barrier to establish systemic infection, and clinical studies indicate virus more easily evades this barrier in women using depot-medroxyprogesterone acetate (DMPA) and other injectable progestins for contraception. Identifying a potential mechanism for this association, we learned DMPA promotes susceptibility of wild-type mice to genital herpes simplex virus type 2 (HSV-2) infection by reducing genital tissue expression of the cell-cell adhesion molecule desmoglein-1 (DSG-1) and increasing genital mucosal permeability...
January 2018: Journal of the International AIDS Society
Robert Pollmann, Thomas Schmidt, Rüdiger Eming, Michael Hertl
Pemphigus is a group of rare, potentially devastating autoimmune diseases of the skin and mucous membranes with high morbidity and potentially lethal outcome. The major clinical variant, pemphigus vulgaris (PV) is caused by a loss of intercellular adhesion of epidermal keratinocytes which is induced by IgG autoantibodies against components of desmosomes. Specifically, IgG against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), preferentially target their ectodomains which are presumably critical for the transinteraction and signalling function of these adhesion molecules...
January 8, 2018: Clinical Reviews in Allergy & Immunology
Christine E Wang, Roma C Yumul, Jonathan Lin, Yilong Cheng, André Lieber, Suzie H Pun
Carcinomas contain tight junctions that can limit the penetration and therefore therapeutic efficacy of anticancer agents, especially those delivered by nano-carrier systems. The junction opener (JO) protein is a virus-derived protein that can transiently open intercellular junctions in epithelial tumors by cleaving the junction protein desmoglein-2 (DSG2). Co-administration of JO was previously shown to significantly increase the efficacy of various monoclonal antibodies and chemotherapy drugs in murine tumor models by allowing for increased intratumoral penetration of the drugs...
January 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Thomas Schmidt, Susanne Mauracher, Lena Bender, Brandon Greene, Jonas Kurzhals, Rüdiger Eming, Ralf Dostatni, Michael Hertl
Pemphigus vulgaris (PV) is a severe autoimmune blistering disease of the skin and mucous membranes. As autoantibodies play an essential role in the disease pathogenesis, the serological detection of anti-desmoglein 3 IgG represents a central tool in the diagnosis of the disease. In this study, we show the validation of a novel lateral flow immunoassay (LFIA) which rapidly detects anti-desmoglein 3 (Dsg3) IgG in human serum. In contrast to other diagnostic procedures, the assay is compact and simple to perform and delivers a fast "yes" or "no" answer within 10 min without additional hardware requirements for test evaluation...
December 26, 2017: Experimental Dermatology
Jouni Uitto
Epidermolysis bullosa (EB) is a heterogeneous group of heritable blistering disorders with considerable morbidity and mortality. Currently, there is no effective treatment or cure for EB, but bone marrow transplantation (BMT) has been suggested to improve the clinical presentation and quality of life in some patients with the recessive dystrophic subtype of EB. In this issue, Hünefeld et al. (pp.000) address the issue whether BMT could be applied to patients with EB simplex with intra-epidermal blistering...
December 16, 2017: Journal of Investigative Dermatology
Melanie K Laird, Hanon McShea, Christopher R Murphy, Bronwyn M McAllan, Geoff Shaw, Marilyn B Renfree, Michael B Thompson
In mammalian pregnancy, the uterus is remodelled to become receptive to embryonic implantation. Since non-invasive placentation in marsupials is likely derived from invasive placentation, and is underpinned by intra-uterine conflict between mother and embryo, species with non-invasive placentation may employ a variety of molecular mechanisms to maintain an intact uterine epithelium and to prevent embryonic invasion. Identifying such modifications to the uterine epithelium of marsupial species with non-invasive placentation is key to understanding how conflict is mediated during pregnancy in different mammalian groups...
December 15, 2017: Molecular Reproduction and Development
Priscilla Walsh, Maria J F Brochado, Sebastian Vernal, Aline R Machado, Aline Turatti, Natalia A de Paula, Eduardo A Donadi, Ana Maria Roselino
Background: Antibodies against Leishmania peptides (Lbr-peps) and desmogleins (Dsgs) have been reported in pemphigus foliaceus (PF) and leishmaniasis patients, respectively. We aimed to compare serological and genetic features in a Brazilian region endemic for American tegumentary leishmaniasis (ATL) and pemphigus. Methods: Commercial anti-Dsg ELISA and in-house ELISA with Lbr-peps were used to determine the serological profile, in addition to immunoblotting (IB) and indirect immunofluorescence (IIF) assays...
August 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
Futoshi Muranaka, Tomoyuki Nakajima, Mai Iwaya, Keiko Ishii, Kayoko Higuchi, Naoko Ogiwara, Shinichi Miyagawa, Hiroyoshi Ota
To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining...
December 12, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
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