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Psoriasis and gene therapy

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https://www.readbyqxmd.com/read/28505128/a-proposal-for-a-study-on-treatment-selection-and-lifestyle-recommendations-in-chronic-inflammatory-diseases-a-danish-multidisciplinary-collaboration-on-prognostic-factors-and-personalised-medicine
#1
Vibeke Andersen, Uffe Holmskov, Signe Bek Sørensen, Mohamad Jawhara, Karina W Andersen, Anette Bygum, Lone Hvid, Jakob Grauslund, Jimmi Wied, Henning Glerup, Ulrich Fredberg, Jan Alexander Villadsen, Søren Geill Kjær, Jan Fallingborg, Seyed A G R Moghadd, Torben Knudsen, Jacob Brodersen, Jesper Frøjk, Jens F Dahlerup, Ole Haagen Nielsen, Robin Christensen, Anders Bo Bojesen, Grith Lykke Sorensen, Steffen Thiel, Nils J Færgeman, Ivan Brandslund, Allan Stensballe, Erik Berg Schmidt, Andre Franke, David Ellinghaus, Philip Rosenstiel, Jeroen Raes, Berit Heitmann, Mette Boye, Charlotte Lindgaard Nielsen, Lars Werner, Jens Kjeldsen, Torkell Ellingsen
Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome...
May 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28489810/a-case-report-of-hereditary-neuropathy-with-liability-to-pressure-palsies-accompanied-by-type-2-diabetes-mellitus-and-psoriasis
#2
Jing Li, Bing Niu, Xiaoling Wang, Huaiqiang Hu, Bingzhen Cao
RATIONALE: Hereditary neuropathy with liability to pressure palsy (HNPP) is an episodic, multifocal neuropathy, with a typical clinical presentation of recurrent transient pressure palsies, which is induced by a PMP22 deletion. Another neuropathy caused by a PMP22 duplication is Charcot-Marie-Tooth disease type 1A (CMT1A). PMP22 is a gene coding a protein called peripheral myelin protein 22 (PMP22), which plays an essential role in the formation and maintenance of compact myelin. Coexistence of type 2 diabetes mellitus (T2DM) and CMT1A has been reported in many work, however HNPP patients with T2DM are rare, and comorbidity of HNPP and psoriasis has not been reported previously...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28444425/pharmacogenetic-markers-to-predict-the-clinical-response-to-methotrexate-in-south-indian-tamil-patients-with-psoriasis
#3
S Indhumathi, Medha Rajappa, Laxmisha Chandrashekar, P H Ananthanarayanan, D M Thappa, V S Negi
INTRODUCTION: Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. OBJECTIVES: We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis...
April 25, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28412864/cutaneous-allergic-drug-reactions-update-on-pathophysiology-diagnostic-procedures-and-differential-diagnostic
#4
Galina Balakirski, Hans F Merk
Important changes in the understanding and management of drug hypersensitivity reactions during the last years result from the increasing importance of biologics in medical practice, which differ in their spectrum of adverse drug reactions (ADRs) from the classical covalent drugs. With regard to covalent drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause of anaphylactic and photosensitivity reactions...
April 17, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/28397054/effects-of-rna-interference-combined-with-ultrasonic-irradiation-and-sonovue-microbubbles-on-expression-of-stat3-gene-in-keratinocytes-of-psoriatic-lesions
#5
Li-Wei Ran, Hao Wang, Dong Lan, Hong-Xia Jia, Si-Si Yu
The most effective sequence of small interfering RNA (siRNA) silencing STAT3 of psoriatic keratinocytes (KCs) was screened out, and the effects of the most effective siRNA combined with ultrasonic irradiation and SonoVue microbubbles on the expression of STAT3 of KCs and the dose- and time-response were investigated. Three chemically-synthetic siRNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs, and the effects on STAT3 expression were detected, then the most effective siRNA was selected for the subsequent experiments...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28239073/effects-of-topical-application-of-betamethasone-on-imiquimod-induced-psoriasis-like-skin-inflammation-in-mice
#6
Hiroki Mori, Kojo Arita, Takayuki Yamaguchi, Midori Hirai, Yoichi Kurebayashi
Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis therapy, we investigated the effect of betamethasone ointment on imiquimod (IMQ)-induced skin inflammation in mice. In BALB/c mice, topical IMQ at the dose of 250 µg each on both sides of the ear induced marked psoriasis-like skin inflammation within 5 days. The same dose of IMQ produced only slight to moderate skin inflammation even on Day 7 in CB-17 scid mice...
September 9, 2016: Kobe Journal of Medical Sciences
https://www.readbyqxmd.com/read/28168735/does-imiquimod-pretreatment-optimize-308-nm-excimer-laser-uvb-therapy-in-psoriasis-patients
#7
Joselin D Tacastacas, Patricia Oyetakin-White, David C Soler, Andrew Young, Sarah Groft, Kord Honda, Kevin D Cooper, Thomas S McCormick
BACKGROUND/PURPOSE: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. AIMS/OBJECTIVES: In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques...
February 7, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/28109175/langerhans-cell-markers-cd1a-and-cd207-are-the-most-rapidly-responding-genes-in-lesional-psoriatic-skin-following-adalimumab-treatment
#8
Line Raaby, Cecilia Rosada, Ane Langkilde, Kristina Lystlund Lauridsen, Hanne Vinter, Pernille Ommen, Rasmus Boye Kjellerup, Claus Johansen, Lars Iversen
TNFα-, IL-23- and IL-17-targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells (LCs) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL-23/IL-17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL-17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air-liquid interphase for 4 days...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28043870/il-1-and-il-36-are-dominant-cytokines-in-generalized-pustular-psoriasis
#9
Andrew Johnston, Xianying Xing, Liza Wolterink, Drew H Barnes, ZhiQiang Yin, Laura Reingold, J Michelle Kahlenberg, Paul W Harms, Johann E Gudjonsson
BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, debilitating, and often life-threatening inflammatory disease characterized by episodic infiltration of neutrophils into the skin, pustule development, and systemic inflammation, which can manifest in the presence or absence of chronic plaque psoriasis (PV). Current treatments are unsatisfactory and warrant a better understanding of GPP pathogenesis. OBJECTIVE: We sought to understand better the disease mechanism of GPP to allow improved targeted therapies...
December 31, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28027921/t-helper-2-cytokine-regulatory-t-cell-gene-polymorphisms-and-their-relation-with-risk-of-psoriasis-in-a-south-indian-tamil-cohort
#10
Sundar Indhumathi, Medha Rajappa, Laxmisha Chandrashekar, Palghat Hariharan Ananthanarayanan, Devinder Mohan Thappa, Vir Singh Negi
BACKGROUND: Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils...
February 2017: Human Immunology
https://www.readbyqxmd.com/read/27910163/serum-amyloid-a-an-acute-phase-protein-stimulates-proliferative-and-proinflammatory-responses-of-keratinocytes
#11
Ning Yu, Shujie Zhang, Jiajing Lu, Ying Li, Xuemei Yi, Li Tang, Lina Su, Yangfeng Ding
OBJECTIVES: Serum amyloid A (SAA), an acute phase protein, is highly expressed in psoriatic lesions but its function is not fully understood. The aim of this study was to explore its role in activation of keratinocytes. MATERIALS AND METHODS: Real-time PCR and immunofluorescence were performed to examine SAA expression in imiquimod (IMQ)-induced psoriasis-like mice. In vivo function of SAA was examined by treating psoriasis-like mice with SAA neutralising antibody...
June 2017: Cell Proliferation
https://www.readbyqxmd.com/read/27892584/a-short-history-of-phototherapy-vitamin-d-and-skin-disease
#12
Paul Jarrett, Robert Scragg
The earliest record between sun exposure and skin disease goes back five millennia to the ancient Egyptians. The modern scientific era of medical light therapy and skin diseases started in 1877 when Downs and Blunt reported that exposure to light inhibited fungal growth in test tubes. Continuing research generated a growing medical interest in the potential the effects of light to treat and cure skin diseases considered as parasitic. This culminated in the awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering work showing that light could successfully treat cutaneous mycobacterium tuberculosis (lupus vulgaris), a disfiguring disorder common at the time...
March 16, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/27853279/controlled-mycobacterium-tuberculosis-infection-in-mice-under-treatment-with-anti-il-17a-or-il-17f-antibodies-in-contrast-to-tnf%C3%AE-neutralization
#13
Noria Segueni, Elaine Tritto, Marie-Laure Bourigault, Stéphanie Rose, François Erard, Marc Le Bert, Muazzam Jacobs, Franco Di Padova, Daniel P Stiehl, Pierre Moulin, Dominique Brees, Salah-Dine Chibout, Bernhard Ryffel, Michael Kammüller, Valerie F Quesniaux
Antibodies targeting IL-17A or its receptor IL-17RA show unprecedented efficacy in the treatment of autoimmune diseases such as psoriasis. These therapies, by neutralizing critical mediators of immunity, may increase susceptibility to infections. Here, we compared the effect of antibodies neutralizing IL-17A, IL-17F or TNFα on murine host responses to Mycobacterium tuberculosis infection by evaluating lung transcriptomic, microbiological and histological analyses. Coinciding with a significant increase of mycobacterial burden and pathological changes following TNFα blockade, gene array analyses of infected lungs revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799070/capture-hi-c-identifies-a-novel-causal-gene-il20ra-in-the-pan-autoimmune-genetic-susceptibility-region-6q23
#14
Amanda McGovern, Stefan Schoenfelder, Paul Martin, Jonathan Massey, Kate Duffus, Darren Plant, Annie Yarwood, Arthur G Pratt, Amy E Anderson, John D Isaacs, Julie Diboll, Nishanthi Thalayasingam, Caroline Ospelt, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk...
November 1, 2016: Genome Biology
https://www.readbyqxmd.com/read/27783430/roles-of-micrornas-in-psoriasis-immunological-functions-and-potential-biomarkers
#15
REVIEW
Qing Liu, Ding-Hong Wu, Ling Han, Jing-Wen Deng, Li Zhou, Rui He, Chuan-Jian Lu, Qing-Sheng Mi
MicroRNAs (miRNAs) are small non-coding RNA molecules, which function in RNA silencing and post-transcriptional regulation of gene expression. Psoriasis is an inflammatory skin disease characterized by the dysfunction of keratinocytes, with the immune dysregulation. We reviewed the recent studies on the roles of miRNAs in psoriasis and showed that miRNAs play key roles in psoriasis, including the regulation of hyperproliferation, cytokine and chemokine production in keratinocyte, as well as mediating immune dysfunction in psoriasis...
April 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/27774581/a-preliminary-study-of-new-single-polymorphisms-in-the-t-helper-type-17-pathway-for-psoriasis-in-the-korean-population
#16
S Y Kim, M S Hur, B G Choi, M J Kim, Y W Lee, Y B Choe, K J Ahn
Psoriasis is a polygenic and multi-factorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin (IL)-17A, IL-17 receptor (IL-17R) and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper type 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis...
February 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27670766/il17ra-gene-variants-and-anti-tnf-response-among-psoriasis-patients
#17
A Batalla, E Coto, J Gómez, N Eirís, D González-Fernández, C Gómez-De Castro, E Daudén, M Llamas-Velasco, R Prieto-Perez, F Abad-Santos, G Carretero, F S García, Y B Godoy, L F Cardo, B Alonso, S Iglesias, P Coto-Segura
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months...
September 27, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27641916/functional-genomics-and-its-bench-to-bedside-translation-pertaining-to-the-identified-susceptibility-alleles-and-loci-in-ankylosing-spondylitis
#18
REVIEW
Tony J Kenna, Aimee Hanson, Mary-Ellen Costello, Matthew A Brown
Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway...
October 2016: Current Rheumatology Reports
https://www.readbyqxmd.com/read/27639151/droplet-digital-pcr-analysis-of-gstm1-deletion-polymorphism-in-psoriatic-subjects-treated-with-goeckerman-therapy
#19
Martin Beránek, Zdeněk Fiala, Jan Kremláček, Ctirad Andrýs, Květoslava Hamáková, Vladimír Palička, Lenka Borská
Goeckerman therapy (GT) represents an effective treatment of psoriasis including a combination of pharmaceutical grade crude coal tar (CCT) and ultraviolet irradiation (UV-R). Coal tar contains a mixture of polycyclic aromatic hydrocarbons. The best known carcinogenic polyaromate - benzo[a]pyrene is metabolized into a highly reactive benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Glutathione S-transferase M1 (GSTM1) catalyses the conjugation of drugs, toxins and products of oxidative stress with glutathione. The aim of the study is to found possible associations between GSTM1 genotypes and the level of BPDE-DNA adducts in 46 psoriatic patients treated with GT...
2016: Acta Medica (Hradec Králové)
https://www.readbyqxmd.com/read/27627098/biomolecular-index-of-therapeutic-efficacy-in-psoriasis-treated-by-anti-tnf-alpha-agents
#20
Luca Bianchi, Gaetana Costanza, Elena Campione, Manuela Ruzzetti, Alessandro Di Stefani, Laura Diluvio, Emiliano Giardina, Raffaella Cascella, Paola Cordiali-Fei, Claudio Bonifati, Andrea Chiricozzi, Giuseppe Novelli, Fabrizio Ensoli, Augusto Orlandi
BACKGROUND: Clinical or quality of life assessments are currently available for psoriasis severity evaluation and therapeutic response. Laboratory scores focused to measure and follow treatment efficacy are lacking at present. METHODS: Design a microscopic and biomolecular score to monitor skin disease severity and clinical response to anti-psoriatic treatments. A susceptibility gene analysis on cellular retinoic acid binding protein-II (CRABP-II), acting on keratinocyte differentiation, was also performed...
September 14, 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
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