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https://www.readbyqxmd.com/read/29313220/pemphigus-a-comprehensive-review-on-pathogenesis-clinical-presentation-and-novel-therapeutic-approaches
#1
REVIEW
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
https://www.readbyqxmd.com/read/29305923/junction-opener-protein-increases-nanoparticle-accumulation-in-solid-tumors
#2
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
https://www.readbyqxmd.com/read/29278440/a-novel-lateral-flow-immunoassay-for-the-rapid-detection-of-anti-dsg3-igg-serum-autoantibodies-in-pemphigus-vulgaris
#3
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
https://www.readbyqxmd.com/read/29258894/the-conundrum-of-allogeneic-bone-marrow-transplantation-for-epidermolysis-bullosa
#4
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
https://www.readbyqxmd.com/read/29243855/non-invasive-placentation-in-the-marsupials-macropus-eugenii-macropodidae-and-trichosurus-vulpecula-phalangeridae-involves-redistribution-of-uterine-desmoglein-2
#5
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
https://www.readbyqxmd.com/read/29237064/relationship-between-pemphigus-and-american-tegumentary-leishmaniasis-insights-from-serological-and-genetic-profiles
#6
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...
December 11, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29232767/a-comparative-immunohistochemical-study-of-anal-canal-epithelium-in-humans-and-swine-focusing-on-the-anal-transitional-zone-epithelium-and-the-anal-glands
#7
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
https://www.readbyqxmd.com/read/29214101/cell-junction-protein-armadillo-repeat-gene-deleted-in-velo-cardio-facial-syndrome-is-expressed-in-the-skin-and-colocalizes-with-autoantibodies-of-patients-affected-by-a-new-variant-of-endemic-pemphigus-foliaceus-in-colombia
#8
Ana Maria Abreu-Velez, Hong Yi, Michael S Howard
Background: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF, or pemphigus Abreu-Manu). El Bagre-EPF differs from other types of EPF clinically, epidemiologically, immunologically and in its target antigens. We reported the presence of patient autoantibodies colocalizing with armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), a catenin cell junction protein colocalizing with El Bagre-EPF autoantibodies in the heart and within pilosebaceous units along their neurovascular supply routes...
October 2017: Dermatology Practical & Conceptual
https://www.readbyqxmd.com/read/29212005/desmoglein-3-order-and-dynamics-in-desmosomes-determined-by-fluorescence-polarization-microscopy
#9
Emily I Bartle, Tara M Urner, Siddharth S Raju, Alexa L Mattheyses
Desmosomes are macromolecular cell-cell junctions that provide adhesive strength in epithelial tissue. Desmosome function is inseparably linked to structure, and it is hypothesized that the arrangement, or order, of desmosomal cadherins in the intercellular space is critical for adhesive strength. However, due to desmosome size, molecular complexity, and dynamics, the role that order plays in adhesion is challenging to study. Herein, we present an excitation resolved fluorescence polarization microscopy approach to measure the spatiotemporal dynamics of order and disorder of the desmosomal cadherin desmoglein 3 (Dsg3) in living cells...
December 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29203359/bone-marrow-derived-stem-cells-migrate-into-intra-epidermal-skin-defects-of-a-desmoglein-3-knockout-mouse-model-but-preserve-their-mesodermal-differentiation
#10
Christian Hünefeld, Markus Mezger, Eva Müller-Hermelink, Martin Schaller, Ingo Müller, Masayuki Amagai, Rupert Handgretinger, Martin Röcken
Inherited forms of Epidermolysis bullosa (EB) are blistering diseases of the skin and mucosa resulting from various gene mutations. Transplantation of bone marrow (BM)-derived stem cells might be a promising systemic treatment for severe dystrophic or junctional EB, but many key questions remain unresolved. Two open questions of clinical interest are whether systemically transplanted BM-derived stem cells of mesodermal origin might be able to transdifferentiate into keratinocytes with an ectodermal phenotype and whether these cells are also capable of repairing a specific intra-epidermal gene defect...
December 1, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29198699/activation-of-pkb-akt-and-p44-42-by-mechanical-stretch-utilizes-desmosomal-structures-and-the-keratin-filament
#11
Stefan Kippenberger, Johannes Kleemann, Markus Meissner, Katja Steinhorst, Jutta Müller, Christos C Zouboulis, Roland Kaufmann, Nadja Zöller
BACKGROUND: Mechanical stress is an ubiquitous challenge of human cells with fundamental impact on cell physiology. Previous studies have shown that stretching promotes signalling cascades involved in proliferation and tissue enlargement. OBJECTIVE: The present study is dedicated to learn more about cellular structures contributing to perception and signal transmission of cell stretch. In particular, we hypothesized that desmosmal contacts and the adjacent keratin filament build an intercellular matrix providing information about the mechanical load...
November 30, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29178656/unique-genetic-background-and-outcome-of-non-caucasian-japanese-probands-with-arrhythmogenic-right-ventricular-dysplasia-cardiomyopathy
#12
Yuko Wada, Seiko Ohno, Takeshi Aiba, Minoru Horie
BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy mainly caused by desmosomal gene mutation. More than half of Caucasian probands have desmosomal mutations, which lead to earlier onset of ventricular arrhythmias. Among non-Caucasians, the genetic background of ARVD/C probands and its prognostic impact remain unclear. METHODS AND RESULTS: We genotyped 99 unrelated Japanese ARVD/C probands for plakophilin 2 (PKP2), desmoglein 2 (DSG2), desmoplakin (DSP), and desmocollin 2 (DSC2) between 2005 and 2014...
November 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29159879/new-insights-into-pemphigoid-diseases
#13
Frank Antonicelli, Ralf J Ludwig
Pemphigus and pemphigoid diseases are organ-specific autoimmune blistering diseases (AIBD), characterized and caused by autoantibodies to structural components of the skin (1). The autoantigens targeted in pemphigus are desmoglein 1 and 3, two proteins of the desmosomal structure, while the autoantigens in pemphigoid diseases (PD) are components of the basal membrane. For example, bullous pemphigoid (BP), the most frequent PD is characterized by autoantibodies against type XVII collagen (COL17, BP180) and BP230, and epidermolysis bullosa acquisita (EBA) is caused by autoantibodies against type VII collagen (COL7)...
November 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29152726/autoantibodies-to-full-body-vascular-cell-junctions-colocalize-with-myzap-arvcf-desmoplakins-i-and-ii-and-p0071-in-endemic-pemphigus-in-colombia-south-america
#14
Ana M Abreu Velez, Hong Yi, Gunnar Warfvinge, Michael S Howard
BACKGROUND: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF). METHODS: Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies...
November 20, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/29145342/evaluation-of-anti-desmoglein-1-and-anti-desmoglein-3-autoantibody-titers-in-pemphigus-patients-at-the-time-of-the-initial-diagnosis-and-after-clinical-remission
#15
Irene Russo, Francesco Paolo De Siena, Andrea Saponeri, Mauro Alaibac
It has been suggested that anti-desmoglein autoantibody titers could be helpful in follow-up and therapeutic management of pemphigus patients. However, there is no consensus regarding the relationship between anti-desmoglein autoantibody titers and clinical activity of pemphigus.The aim of our study was to evaluate if clinical remission of pemphigus relates to the presence of anti-desmoglein autoantibodies.Thirty patients with pemphigus vulgaris and 7 patients with pemphigus foliaceous were included in the study...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29132070/sixteen-year-history-of-rituximab-therapy-for-1085-pemphigus-vulgaris-patients-a-systematic-review
#16
REVIEW
Soheil Tavakolpour, HamidReza Mahmoudi, Kamran Balighi, Robabeh Abedini, Maryam Daneshpazhooh
Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria...
November 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29096849/successful-and-well-tolerated-bi-weekly-immunoadsorption-regimen-in-pemphigus-vulgaris
#17
Jenny Dietze, Bernd Hohenstein, Sergey Tselmin, Ulrich Julius, Stefan R Bornstein, Stefan Beissert, Claudia Günther
BACKGROUND: Pemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect keratinocytes in the epidermis. Autoantibody deposition in the skin causes inflammation and intraepidermal akantholysis. The concentration of autoantibodies in serum correlates with disease activity...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29069744/eight-potential-biomarkers-for-distinguishing-between-lung-adenocarcinoma-and-squamous-cell-carcinoma
#18
Jian Xiao, Xiaoxiao Lu, Xi Chen, Yong Zou, Aibin Liu, Wei Li, Bixiu He, Shuya He, Qiong Chen
Lung adenocarcinoma (LADC) and squamous cell carcinoma (LSCC) are the most common non-small cell lung cancer histological phenotypes. Accurate diagnosis distinguishing between these two lung cancer types has clinical significance. For this study, we analyzed four Gene Expression Omnibus (GEO) datasets (GSE28571, GSE37745, GSE43580, and GSE50081). We then imported the datasets into the Gene-Cloud of Biotechnology Information online platform to identify genes differentially expressed in LADC and LSCC. We identified DSG3 (desmoglein 3), KRT5 (keratin 5), KRT6A (keratin 6A), KRT6B (keratin 6B), NKX2-1 (NK2 homeobox 1), SFTA2 (surfactant associated 2), SFTA3 (surfactant associated 3), and TMC5 (transmembrane channel-like 5) as potential biomarkers for distinguishing between LADC and LSCC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29064314/rituximab-in-pemphigus
#19
Vivien Hebert, Pascal Joly
Pemphigus is a severe autoimmune blistering disease mediated by pathogenic anti-desmoglein antibodies leading to an inter keratinocyte disjunction. Rituximab is a monoclonal antibody that binds to the CD-20 antigen of B lymphocytes, which causes B-cell depletion and a subsequent reduction in pathogenic autoantibodies. Its therapeutic role in pemphigus has been progressively growing with increasing evidence of successful outcomes. Rituximab was initially off-labeled used as an alternative in patients with recalcitrant or relapsing pemphigus and in patients with contraindications to systemic corticosteroids...
October 24, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29062102/arrhythmogenic-cardiomyopathy-related-dsg2-mutations-affect-desmosomal-cadherin-binding-kinetics
#20
Mareike Dieding, Jana Davina Debus, Raimund Kerkhoff, Anna Gaertner-Rommel, Volker Walhorn, Hendrik Milting, Dario Anselmetti
Cadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging the gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. Here, we investigated the homophilic binding of wildtype Dsg2 and two mutations which are associated with ARVC...
October 23, 2017: Scientific Reports
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