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https://www.readbyqxmd.com/read/29132070/sixteen-year-history-of-rituximab-therapy-for-1085-pemphigus-vulgaris-patients-a-systematic-review
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/29055412/desmoglein-3-reactive-b-cells-hiding-in-pemphigus-lesions
#6
Hayato Takahashi
Pemphigus vulgaris is an autoimmune blistering disease caused by anti-desmoglein 3 IgG autoantibodies. It is accepted that interactions between autoreactive B and T cells are key to humoral autoimmunity targeting desmoglein 3. This orchestrated process usually occurs in secondary lymphoid organs, including the spleen and lymph nodes. Thus, it seems likely that autoreactive B cells reside and produce autoantibodies in these tissues. Yuan et al. analyzed lymphocytes in the lesional skin of patients with pemphigus vulgaris using several experimental techniques and concluded that desmoglein 3-reactive B cells were present...
November 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29038103/large-genomic-rearrangements-of-desmosomal-genes-in-italian-arrhythmogenic-cardiomyopathy-patients
#7
Kalliopi Pilichou, Elisabetta Lazzarini, Ilaria Rigato, Rudy Celeghin, Marzia De Bortoli, Marina Perazzolo Marra, Marco Cason, Jan Jongbloed, Martina Calore, Stefania Rizzo, Daniela Regazzo, Giulia Poloni, Sabino Iliceto, Luciano Daliento, Pietro Delise, Domenico Corrado, J Peter Van Tintelen, Gaetano Thiene, Alessandra Rampazzo, Cristina Basso, Barbara Bauce, Alessandra Lorenzon, Gianluca Occhi
BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disease associated with point mutations in genes encoding for cardiac desmosome proteins. Conventional mutation screening is positive in ≈50% of probands. Copy number variations (CNVs) have recently been linked to AC pointing to the need to determine the prevalence of CNVs in desmosomal genes and to evaluate disease penetrance by cosegregation analysis in family members. METHODS AND RESULTS: A total of 160 AC genotype-negative probands for 5 AC desmosomal genes by conventional mutation screening underwent multiplex ligation-dependent probe amplification...
October 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29037765/mechanisms-causing-loss-of-keratinocyte-cohesion-in-pemphigus
#8
REVIEW
Volker Spindler, Rüdiger Eming, Enno Schmidt, Masayuki Amagai, Sergei Grando, Marcel F Jonkman, Andrew P Kowalczyk, Eliane J Müller, Aimee S Payne, Carlo Pincelli, Animesh A Sinha, Eli Sprecher, Detlef Zillikens, Michael Hertl, Jens Waschke
The autoimmune blistering skin disease pemphigus is caused by IgG autoantibodies against desmosomal cadherins, but the precise mechanisms are in part a matter of controversial discussions. This review focuses on the currently existing models of the disease and highlights the relevance of desmoglein-specific versus nondesmoglein autoantibodies, the contribution of nonautoantibody factors, and the mechanisms leading to cell dissociation and blister formation in response to autoantibody binding. As the review brings together the majority of laboratories currently working on pemphigus pathogenesis, it aims to serve as a solid basis for further investigations for the entire field...
October 13, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29025244/a-comparative-study-of-expression-of-fc-receptors-in-relation-to-the-autoantibody-mediated-immune-response-and-neutrophil-elastase-expression-in-autoimmune-blistering-dermatoses
#9
Justyna Gornowicz-Porowska, Agnieszka Seraszek-Jaros, Monika Bowszyc-Dmochowska, Elżbieta Kaczmarek, Paweł Pietkiewicz, Paweł Bartkiewicz, Marian Dmochowski
Here we investigated the cutaneous CD32A and CD89 expression in relation to the neutrophil elastase (NE) expression and serum level of anti-desmoglein 1 and 3 (DSG1/DSG3) IgG in pemphigus, anti-BP180/BP230 IgG in bullous pemphigoid (BP), anti-gliadin nonapeptides (npG), tissue (tTG), and epidermal transglutaminases (eTG) IgA in dermatitis herpetiformis (DH). The examined material consisted of skin/mucosal tissues and sera. In total, 87 patients were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of CD32A/CD89/NE expressions...
2017: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
https://www.readbyqxmd.com/read/28979862/comparison-of-direct-immunofluorescence-of-plucked-hair-and-skin-for-evaluation-of-immunological-remission-in-pemphigus
#10
Reena Rai, Manu V Harikumar
BACKGROUND: Pemphigus is a chronic autoimmune bullous disorder characterized by autoantibodies directed against desmoglein 3 and/or 1. Demonstration of intercellular deposition of IgG on the cell surface of keratinocytes by direct immunofluorescence (DIF) of the skin is the gold standard in the diagnosis of pemphigus. Recently, DIF of plucked hair demonstrating intercellular deposition of IgG in the outer root sheath (ORS) has shown to be useful. OBJECTIVE: To compare the DIF of plucked hair and skin for the evaluation of immunological remission in pemphigus vulgaris patients in clinical remission...
September 2017: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/28948640/clinical-evaluation-of-a-multiparametric-elisa-as-a-rapid-tool-for-routinely-diagnosing-igg-mediated-autoimmune-blistering-dermatoses-in-ethnic-slavs
#11
Justyna Gornowicz-Porowska, Agnieszka Seraszek-Jaros, Monika Bowszyc-Dmochowska, Paweł Bartkiewicz, Elżbieta Kaczmarek, Marian Dmochowski
BACKGROUND: Technical innovation of autoimmune blistering dermatoses (ABDs) diagnosis aimed at multiplex approach. Two multiparametric ELISA tests are commercially available for ABDs serology. The aim was to compare diagnostic accuracy of multiparametric and monospecific ELISAs and to examine the diagnostic value/agreement of multivariant ELISA in compliance with traditional diagnostic setup for ABDs. METHODS: In total, 128 sera from suspected ABDs patients were studied (27 sera in order to compare ELISAs)...
September 26, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28932036/current-concepts-of-pemphigus-with-a-deep-insight-into-its-molecular-aspects
#12
REVIEW
Jayakiran Madala, Rithika Bashamalla, M Praveen Kumar
Pemphigus vulgaris is an autoimmune bullous disease involving both the skin and mucosal areas, which is characterized by intraepithelial flaccid blisters and erosions. The pathogenesis of this disease is not yet completely established, but novel intuitions into its pathogenesis have recently been published. An unanswered question in its pathophysiology is the mechanism of acantholysis or loss of keratinocyte cell adhesion. Acantholysis seems to result from a communal action of autoantibodies against numerous keratinocyte self-antigens, of which desmogleins 1 and 3, desmocollins and nondesmosome components, such as the mitochondrion, might take part in the disease initiation...
May 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28928959/cell-polarity-cell-adhesion-and-spermatogenesis-role-of-cytoskeletons
#13
REVIEW
Linxi Li, Ying Gao, Haiqi Chen, Tito Jesus, Elizabeth Tang, Nan Li, Qingquan Lian, Ren-Shan Ge, C Yan Cheng
In the rat testis, studies have shown that cell polarity, in particular spermatid polarity, to support spermatogenesis is conferred by the coordinated efforts of the Par-, Crumbs-, and Scribble-based polarity complexes in the seminiferous epithelium. Furthermore, planar cell polarity (PCP) is conferred by PCP proteins such as Van Gogh-like 2 (Vangl2) in the testis. On the other hand, cell junctions at the Sertoli cell-spermatid (steps 8-19) interface are exclusively supported by adhesion protein complexes (for example, α6β1-integrin-laminin-α3,β3,γ3 and nectin-3-afadin) at the actin-rich apical ectoplasmic specialization (ES) since the apical ES is the only anchoring device in step 8-19 spermatids...
2017: F1000Research
https://www.readbyqxmd.com/read/28928733/crosstalk-between-signaling-pathways-in-pemphigus-a-role-for-endoplasmic-reticulum-stress-in-p38-mitogen-activated-protein-kinase-activation
#14
Gabriel A Cipolla, Jong Kook Park, Robert M Lavker, Maria Luiza Petzl-Erler
Pemphigus consists of a group of chronic blistering skin diseases mediated by autoantibodies (autoAbs). The dogma that pemphigus is caused by keratinocyte dissociation (acantholysis) as a distinctive and direct consequence of the presence of autoAb targeting two main proteins of the desmosome-desmoglein (DSG) 1 and/or DSG3-has been put to the test. Several outside-in signaling events elicited by pemphigus autoAb in keratinocytes have been described, among which stands out p38 mitogen-activated protein kinase (p38 MAPK) engagement and its apoptotic effect on keratinocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28927663/developing-biomarkers-for-predicting-clinical-relapse-in-pemphigus-patients-treated-with-rituximab
#15
Lauren N Albers, Yuan Liu, Na Bo, Robert A Swerlick, Ron J Feldman
BACKGROUND: Rituximab is an effective therapy for pemphigus, although relapses are common. OBJECTIVE: To identify biomarkers to predict relapse of pemphigus following rituximab treatment. METHODS: In this retrospective cohort study, 62 patients with pemphigus treated with 99 rituximab cycles provided longitudinal clinical scoring and biomarker data, including levels of CD19(+) B cells, CD4(+) T cells, and desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) autoantibodies...
December 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28926939/kempopeptin-c-a-novel-marine-derived-serine-protease-inhibitor-targeting-invasive-breast-cancer
#16
Fatma H Al-Awadhi, Lilibeth A Salvador, Brian K Law, Valerie J Paul, Hendrik Luesch
Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC50 values of 0...
September 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28899688/keratins-regulate-the-adhesive-properties-of-desmosomal-cadherins-through-signaling
#17
Franziska Vielmuth, Marie-Therès Wanuske, Mariya Y Radeva, Matthias Hiermaier, Daniela Kugelmann, Elias Walter, Fanny Buechau, Thomas M Magin, Jens Waschke, Volker Spindler
Tightly controlled intercellular adhesion is crucial for integrity and function of the epidermis. The keratin filament cytoskeleton anchors desmosomes, supramolecular complexes required for strong intercellular adhesion. We here tested whether keratin filaments control cell adhesion by regulating the adhesive properties of desmosomal cadherins such as desmoglein (Dsg) 3. Atomic force microscopy (AFM) and FRAP experiments revealed reduced Dsg3 adhesive forces and membrane stability in murine keratinocytes lacking all keratin filaments...
September 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28899010/modelling-apoe-%C3%A9-3-4-allele-associated-sporadic-alzheimer-s-disease-in-an-induced-neuron
#18
Hongwon Kim, Junsang Yoo, Jaein Shin, Yujung Chang, Junghyun Jung, Dong-Gyu Jo, Janghwan Kim, Wonhee Jang, Christopher J Lengner, Byung-Soo Kim, Jongpil Kim
The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's disease risk factor apolipoprotein E (APOE) ɛ3/4 allele. We show that mouse and human induced neurons overexpressing mutant amyloid precursor protein in the background of APOE ɛ3/4 allele exhibit altered amyloid precursor protein (APP) processing, abnormally increased production of amyloid-β42 and hyperphosphorylation of tau...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28888784/malignant-ascites-determine-the-transmesothelial-invasion-of-ovarian-cancer-cells
#19
Justyna Mikuła-Pietrasik, Paweł Uruski, Sebastian Szubert, Dariusz Szpurek, Stefan Sajdak, Andrzej Tykarski, Krzysztof Książek
The exact role of malignant ascites in the development of intraperitoneal ovarian cancer metastases remains unclear. In this report we sought to establish if ascites can determine the efficiency of transmesothelial invasion of ovarian cancer cells, and, if so, whether the fluid generated by highly aggressive serous and undifferentiated tumors will promote the invasion more effectively than ascites from less aggressive clear cell and endometrioid cancers. The study showed that the invasion of ovarian cancer cells (SKOV-3 and primary cancer cells) across monolayered peritoneal mesothelial cells was elevated upon mesothelial cell exposure to fluid produced by serous and undifferentiated cancers, as compared with cells subjected to ascites from clear cell and endometrioid tumors...
September 6, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28868524/divergent-specificity-development-of-igg1-and-igg4-autoantibodies-in-endemic-pemphigus-foliaceus-fogo-selvagem
#20
Mike Maldonado, Luis A Diaz, Phillip Prisayanh, Jinsheng Yang, Bahjat F Qaqish, Valeria Aoki, Gunter Hans-Filho, Evandro A Rivitti, Donna A Culton, Ye Qian
We have shown that although the IgG response in fogo selvagem (FS) is mainly restricted to desmoglein (Dsg) 1, other keratinocyte cadherins are also targeted by FS patients and healthy control subjects living in the endemic region of Limão Verde, Brazil (endemic controls). Evaluating nonpathogenic IgG1 and pathogenic IgG4 subclass responses to desmosomal proteins may reveal important differences between pathogenic and nonpathogenic responses, and how these differences relate to the pathogenic IgG4 response and resultant FS...
August 1, 2017: Immunohorizons
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