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https://www.readbyqxmd.com/read/30103046/paraneoplastic-autoimmune-multiorgan-syndrome-pams-beyond-the-single-phenotype-of-paraneoplastic-pemphigus
#1
REVIEW
Kyle T Amber, Manuel Valdebran, Sergei A Grando
Paraneoplastic autoimmune multiorgan syndrome (PAMS) is characterized by a heterogenous group of signs and symptoms including severe desquamative stomatitis, a polymorphous cutaneous eruption, humoral immunity against plakin proteins, contribution of cell-mediated autoimmunity and commonly a progressive respiratory failure. Autoantibodies in PAMS target a wide array of antigens including plakins, cadherins, alpha-2-macroglobulin like 1 (A2ML1), BP180, plakophilin-3, and several neuromuscular antigens. Originally described as paraneoplastic pemphigus in 1990 due to some of its clinical and immunologic similarities to classic pemphigus (pemphigus vulgaris and pemphigus foliaceus), PAMS is a multiorganopathy with several distinct features from these classic forms of pemphigus...
August 10, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29989864/evaluation-of-the-importance-of-immunological-profile-for-pemphigus-vulgaris-in-the-light-of-necessity-to-modify-compensation-theory
#2
Ayşe Öktem, Yıldız Hayran, Pınar İncel Uysal, Ahmet Uğur Atılan, Başak Yalçın
According to the "desmoglein compensation theory," anti-Dsg1 and anti-Dsg3 profiles are crucial for the clinical outcome of pemphigus vulgaris. However, recent studies have highlighted several cases with an incompatibility between the antibody profile and clinical manifestation. Data of 37 patients who had been diagnosed pemphigus vulgaris in our Department between January 2014-June 2016 were retrieved from our clinical database. Patients with ABSIS skin involvement scores, oral mucosa extent and severity scores, anti-Dsg1 and Dsg3 antibody profile were included in this retrospective study...
June 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29989863/salivary-and-serum-anti-desmoglein-1-and-3-elisa-and-indirect-immunofluorescence-in-pemphigus-vulgaris-correlations-with-serum-elisa-indirect-immunofluorescence-and-disease-severity
#3
Maryam Koopai, Hossein Mortazavi, Alireza Khatami, Zohreh Khodashenas
Anti-desmoglein (anti-Dsg) ELISA and indirect immunofluorescence (IIF) are used for the diagnosis of pemphigus vulgaris (PV). The value of salivary ELISA, serum ELISA, and IIF in the diagnosis of PV, and the correlation of salivary anti-Dsg1 and anti-Dsg3 ELISA with serum ELISA, serum and salivary IIF titers, and disease severity in patients with PV were evaluated. Fifty newly diagnosed patients with PV were enrolled in the study. Demographic data and disease-severity scores were recorded for each patient. Anti-Dsg1 and anti-Dsg3 ELISA and IIF were performed on both serum and salivary samples...
June 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29969588/desmoglein-3-influence-on-oral-carcinoma-cell-migration-and-invasion
#4
Ehsanul Hoque Apu, Saad Ullah Akram, Jouni Rissanen, Hong Wan, Tuula Salo
Desmoglein 3 (Dsg3) is an adhesion receptor in desmosomes, but its role in carcinoma cell migration and invasion is mostly unknown. Our aim was to quantitatively analyse the motion of Dsg3-modified carcinoma cells in 2D settings and in 3D within tumour microenvironment mimicking (TMEM) matrices. We tested mutant constructs of C-terminally truncated Dsg3 (∆238 and ∆560), overexpressed full-length (FL) Dsg3, and empty vector control (Ct) of buccal mucosa squamous cell carcinoma (SqCC/Y1) cells. We captured live cell images and analysed migration velocities and accumulated and Euclidean distances...
June 30, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29922278/keratin-retraction-and-desmoglein3-internalization-independently-contribute-to-autoantibody-induced-cell-dissociation-in-pemphigus-vulgaris
#5
Elisabeth Schlögl, Mariya Y Radeva, Franziska Vielmuth, Camilla Schinner, Jens Waschke, Volker Spindler
Pemphigus vulgaris (PV) is a potentially lethal autoimmune disease characterized by blister formation of the skin and mucous membranes and is caused by autoantibodies against desmoglein (Dsg) 1 and Dsg3. Dsg1 and Dsg3 are linked to keratin filaments in desmosomes, adhering junctions abundant in tissues exposed to high levels of mechanical stress. The binding of the autoantibodies leads to internalization of Dsg3 and a collapse of the keratin cytoskeleton-yet, the relevance and interdependence of these changes for loss of cell-cell adhesion and blistering is poorly understood...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29915578/non-desmoglein-antibodies-in-patients-with-pemphigus-vulgaris
#6
REVIEW
Kyle T Amber, Manuel Valdebran, Sergei A Grando
Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease. Patients develop non-healing erosions and blisters due to cell-cell detachment of keratinocytes (acantholysis), with subsequent suprabasal intraepidermal splitting. Identified almost 30 years ago, desmoglein-3 (Dsg3), a Ca2+ -dependent cell adhesion molecule belonging to the cadherin family, has been considered the "primary" autoantigen in PV. Proteomic studies have identified numerous autoantibodies in patients with PV that have known roles in the physiology and cell adhesion of keratinocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29872685/new-biochip-immunofluorescence-test-for-the-serological-diagnosis-of-pemphigus-vulgaris-and-foliaceus-a-review-of-the-literature
#7
REVIEW
Rachel R Xuan, Anes Yang, Dedee F Murrell
The immunoassays that are available for the serological diagnosis of the more common subtypes of autoimmune blistering diseases such as pemphigus vulgaris (PV) and pemphigus foliaceus (PF) include enzyme-linked immunosorbent assay (ELISA) testing to specific antigens desmoglein (Dsg)1 and Dsg3, direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and immunoblotting. A review of the literature on the biochip assay was conducted. Six studies investigated the validity of a new biochip, mosaic-based, IIF test in patients with pemphigus and demonstrated its relatively high sensitivity and specificity (Dsg3: 97...
June 2018: International Journal of Women's Dermatology
https://www.readbyqxmd.com/read/29749496/increased-expression-of-microrna-338-3p-contributes-to-production-of-dsg3-antibody-in-pemphigus-vulgaris-patients
#8
Qingxiu Liu, Feiyi Cui, Menglei Wang, Hao Xiong, Xiaoming Peng, Liuping Liang, Li Li, Jing Zhang, Xuebiao Peng, Kang Zeng
Expression of microRNA-338-3p (miR-338-3p) was aberrantly elevated in pemphigus vulgaris (PV), although its role in PV is still unknown. The present study investigated the functional role and possible molecular mechanisms of miR-338-3p in PV. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-338-3p expression in peripheral blood mononuclear cells (PBMCs) from patients with PV. Correlation with disease severity and anti-desmoglein 3 antibody (anti-Dsg3) titers were analyzed in patients with PV...
July 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29740444/keratinocyte-binding-assay-identifies-anti-desmosomal-pemphigus-antibodies-where-other-tests-are-negative
#9
Federica Giurdanella, Albertine M Nijenhuis, Gilles F H Diercks, Marcel F Jonkman, Hendri H Pas
The serological diagnosis of pemphigus relies on the detection of IgG autoantibodies directed against the epithelial cell surface by indirect immunofluorescence (IIF) on monkey esophagus and against desmoglein 1 (Dsg1) and Dsg3 by ELISA. Although being highly sensitive and specific tools, discrepancies can occur. It is not uncommon that sera testing positive by ELISA give a negative result by IIF and vice versa . This brings diagnostic challenges wherein pemphigus has to be ascertained or ruled out, especially when no biopsy is available...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29616033/keratins-regulate-p38mapk-dependent-desmoglein-binding-properties-in-pemphigus
#10
Franziska Vielmuth, Elias Walter, Michael Fuchs, Mariya Y Radeva, Fanny Buechau, Thomas M Magin, Volker Spindler, Jens Waschke
Keratins are crucial for the anchorage of desmosomes. Severe alterations of keratin organization and detachment of filaments from the desmosomal plaque occur in the autoimmune dermatoses pemphigus vulgaris and pemphigus foliaceus (PF), which are mainly caused by autoantibodies against desmoglein (Dsg) 1 and 3. Keratin alterations are a structural hallmark in pemphigus pathogenesis and correlate with loss of intercellular adhesion. However, the significance for autoantibody-induced loss of intercellular adhesion is largely unknown...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29573413/herpetiform-pemphigus-with-characteristic-transmission-electron-microscopic-findings-of-various-sized-ballooning-vacuoles-in-keratinocytes-without-acantholysis
#11
N Ishiura, M Tamura-Nakano, H Okochi, C Tateishi, M Maki, Y Shimoda, N Ishii, T Hashimoto, T Tamaki
We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various-sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils...
March 24, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29535737/soluble-fas-ligand-is-essential-for-blister-formation-in-pemphigus
#12
Roberta Lotti, En Shu, Tiziana Petrachi, Alessandra Marconi, Elisabetta Palazzo, Marika Quadri, Ann Lin, Lorraine A O'Reilly, Carlo Pincelli
Pemphigus is a blistering disease characterized by pemphigus autoantibodies (PVIgG) directed mostly against desmogleins (Dsgs), resulting in the loss of keratinocyte adhesion (acantholysis). Yet, the mechanisms underlying blister formation remain to be clarified. We have shown previously that anti-Fas ligand (FasL) antibody (Ab) prevents PVIgG-induced caspase-8 activation and Dsg cleavage in human keratinocytes, and that sera from pemphigus patients contain abnormally increased levels of FasL. Here, we demonstrate that recombinant FasL induces the activation of caspases prior to Dsg degradation, and anti-FasL Ab prevents acantholysis in cultured keratinocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29449846/pemphigus-a-disease-of-desmosome-dysfunction-caused-by-multiple-mechanisms
#13
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
https://www.readbyqxmd.com/read/29371917/cell-surface-marker-discovery-for-lung-cancer
#14
Allison S Cohen, Farah K Khalil, Eric A Welsh, Matthew B Schabath, Steven A Enkemann, Andrea Davis, Jun-Min Zhou, David C Boulware, Jongphil Kim, Eric B Haura, David L Morse
Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29313220/pemphigus-a-comprehensive-review-on-pathogenesis-clinical-presentation-and-novel-therapeutic-approaches
#15
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...
February 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29278440/a-novel-lateral-flow-immunoassay-for-the-rapid-detection-of-anti-dsg3-igg-serum-autoantibodies-in-pemphigus-vulgaris
#16
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 minutes without additional hardware requirements for test evaluation...
March 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29258894/the-conundrum-of-allogeneic-bone-marrow-transplantation-for-epidermolysis-bullosa
#17
Jouni Uitto
Epidermolysis bullosa is a heterogeneous group of heritable blistering disorders with considerable morbidity and mortality. Currently, there is no effective treatment or cure for epidermolysis bullosa, but bone marrow transplantation has been suggested to improve the clinical presentation and quality of life of some patients with the recessive dystrophic subtype of epidermolysis bullosa. In this issue, two studies (Hünefeld et al., and Egawa and Kabashima) address the issue whether bone marrow transplantation could be applied to patients with epidermolysis bullosa simplex with intraepidermal blistering...
May 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29237064/relationship-between-pemphigus-and-american-tegumentary-leishmaniasis-insights-from-serological-and-genetic-profiles
#18
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
https://www.readbyqxmd.com/read/29212005/desmoglein-3-order-and-dynamics-in-desmosomes-determined-by-fluorescence-polarization-microscopy
#19
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-intraepidermal-skin-defects-of-a-desmoglein-3-knockout-mouse-model-but-preserve-their-mesodermal-differentiation
#20
Christian Hünefeld, Markus Mezger, Eva Müller-Hermelink, Martin Schaller, Ingo Müller, Masayuki Amagai, Rupert Handgretinger, Martin Röcken
Inherited forms of epidermolysis bullosa are blistering diseases of the skin and mucosa resulting from various gene mutations. Transplantation of bone marrow-derived stem cells might be a promising systemic treatment for severe dystrophic or junctional epidermolysis bullosa, but many key questions remain unresolved. Two open questions of clinical interest are whether systemically transplanted bone marrow-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 intraepidermal gene defect...
May 2018: Journal of Investigative Dermatology
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