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Psoriasis and gene therapy

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https://www.readbyqxmd.com/read/27910163/serum-amyloid-a-an-acute-phase-protein-stimulates-proliferative-and-proinflammatory-responses-of-keratinocytes
#1
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...
December 2, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27892584/a-short-history-of-phototherapy-vitamin-d-and-skin-disease
#2
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...
November 28, 2016: 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
#3
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
#4
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
#5
REVIEW
Qing Liu, Dinghong Wu, Ling Han, Jingwen Deng, Li Zhou, Rui He, Chuanjian 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...
October 26, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27774581/a-preliminary-study-of-new-single-polymorphisms-in-th17-pathway-for-psoriasis-in-the-korean-population
#6
Soo Young Kim, Min Seok Hur, Byung Gon Choi, Min Jung Kim, Yang Won Lee, Yong Beom Choe, Kyu Joong Ahn
Psoriasis is a polygenic and multifactorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin 17A (IL-17A), interleukin 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 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis...
October 24, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27670766/il17ra-gene-variants-and-anti-tnf-response-among-psoriasis-patients
#7
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
#8
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
#9
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...
August 29, 2016: Acta Medica (Hradec Králové)
https://www.readbyqxmd.com/read/27627098/biomolecular-index-of-therapeutic-efficacy-in-psoriasis-treated-by-anti-tnf-alpha-agents
#10
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
https://www.readbyqxmd.com/read/27591988/il17a-and-il17f-gene-polymorphism-association-with-psoriasis-risk-and-response-to-treatment-in-a-polish-population
#11
Monika Białecka, Roksana Ostasz, Mateusz Kurzawski, Adam Klimowicz, Honorata Fabiańczyk, Piotr Bojko, Violetta Dziedziejko, Krzysztof Safranow, Anna Machoy-Mokrzyńska, Marek Droździk
BACKGROUND: Recent studies have revealed the pivotal role of Th17 cells and interleukin-17 (IL-17) in plaque psoriasis development and treatment outcome. The IL-17 family consists of 6 structurally related cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F), of which IL-17A and IL-17F mediate similar biological effects. OBJECTIVES: The aim of this study was to evaluate an association between the IL17A (-197G>A; rs2275913) and IL17F (rs763780: T>C; rs11465553: G>A; rs2397084: T>C) polymorphisms with psoriasis susceptibility as well as response to topical and combined topical with narrow-band ultraviolet B (NB-UVB) therapy in a Polish population...
September 3, 2016: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/27554821/an-il-17-dominant-immune-profile-is-shared-across-the-major-orphan-forms-of-ichthyosis
#12
Amy S Paller, Yael Renert-Yuval, Maria Suprun, Hitokazu Esaki, Margeaux Oliva, Thy Nhat Huynh, Benjamin Ungar, Norma Kunjravia, Rivka Friedland, Xiangyu Peng, Xiuzhong Zheng, Yeriel D Estrada, James G Krueger, Keith A Choate, Mayte Suárez-Fariñas, Emma Guttman-Yassky
BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking, since the underlying molecular basis is poorly understood. OBJECTIVE: To characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsies from 21 genotyped ichthyosis patients (congenital ichthyosiform erythroderma (n=6), lamellar ichthyosis (n=7), epidermolytic ichthyosis, (n=5) and Netherton syndrome (n=3)) by immunohistochemistry and RT-PCR and compared them with healthy controls, and atopic dermatitis (AD) and psoriasis patients...
August 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27524442/gene-polymorphisms-as-predictors-of-response-to-biological-therapies-in-psoriasis-patients
#13
Teresa María Linares-Pineda, Marisa Cañadas-Garre, Antonio Sánchez-Pozo, Miguel Ángel Calleja-Hernández
Psoriasis is a chronic inflammatory autoimmune skin disease, characterized by the formation of erythematous scaly plaques on the skin and joints. The therapies for psoriasis are mainly symptomatic and sometimes with poor response. Response among patients is very variable, especially with biological drugs (adalimumab, etarnecept, infliximab and ustekimumab). This variability may be partly explained by the effect of different genetic backgrounds. This has prompted the investigation of many genes, such as FCGR3A, HLA, IL17F, IL23R, PDE3A-SLCO1C1, TNFα and other associated genes, as potential candidates to predict response to the different biological drugs used for the treatment of psoriasis...
August 12, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27502297/%C3%AE-defensin-2-is-a-responsive-biomarker-of-il-17a-driven-skin-pathology-in-psoriasis
#14
Frank Kolbinger, Christian Loesche, Marie-Anne Valentin, Xiaoyu Jiang, Yi Cheng, Philip Jarvis, Thomas Peters, Claudio Calonder, Gerard Bruin, Florine Polus, Birgit Aigner, David M Lee, Manfred Bodenlenz, Frank Sinner, Thomas Rudolf Pieber, Dhavalkumar D Patel
BACKGROUND: IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. OBJECTIVE: We sought to determine the role of IL-17A in psoriasis pathogenesis, and to identify a robust, measurable biomarker of IL-17A-driven pathology. METHODS: We studied 8 healthy and 8 psoriasis subjects before and after administration of secukinumab, a fully human anti-IL-17A mAb, and utilized a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, non-lesional skin and lesional skin...
August 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27376751/-pruritus-in-psoriasis-profile-and-therapy
#15
A Tsianakas, U Mrowietz
Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life...
August 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/27376466/tnf-%C3%AE-inhibitors-reduce-the-pathological-th1-th17-th2-imbalance-in-cutaneous-mesenchymal-stem-cells-of-psoriasis-patients
#16
A Campanati, M Orciani, R Lazzarini, G Ganzetti, V Consales, G Sorgentoni, R Di Primio, A Offidani
Psoriasis is a disease characterized by an imbalance between Th1 -Th17 and Th2 inflammatory axes, in which Cutaneous Mesenchymal Stem Cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th1 and Th17 cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis, however their effects on MSCs derived from psoriasis patients have been only partially described. Aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of psoriasis patients...
July 4, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27314537/the-effect-of-phototherapy-on-systemic-inflammatory-process-in-patients-with-plaque-psoriasis
#17
Aleksandra Batycka-Baran, Petra Besgen, Ronald Wolf, Jacek C Szepietowski, Joerg C Prinz
Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA)...
August 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27304428/efficacy-and-safety-of-ustekinumab-treatment-in-adults-with-moderate-to-severe-atopic-dermatitis
#18
Saakshi Khattri, Patrick M Brunner, Sandra Garcet, Robert Finney, Steven R Cohen, Margeaux Oliva, Riana Dutt, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xuan Li, Kathleen M Bonifacio, Norma Kunjravia, Israel Coats, Inna Cueto, Patricia Gilleaudeau, Mary Sullivan-Whalen, Mayte Suárez-Fariñas, James G Krueger, Emma Guttman-Yassky
Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. We sought to assess efficacy and safety of ustekinumab in patients with moderate-to-severe AD. In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16 weeks, and last dose at 32 weeks...
June 15, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27266955/pharmacogenetics-and-pharmacogenomics-in-psoriasis-treatment-current-challenges-and-future-prospects
#19
Alison Sutherland, Rebecca J Power, Proton Rahman, Darren D O'Rielly
INTRODUCTION: Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events. AREAS COVERED: This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis...
August 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27234029/cogena-a-novel-tool-for-co-expressed-gene-set-enrichment-analysis-applied-to-drug-repositioning-and-drug-mode-of-action-discovery
#20
Zhilong Jia, Ying Liu, Naiyang Guan, Xiaochen Bo, Zhigang Luo, Michael R Barnes
BACKGROUND: Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context...
2016: BMC Genomics
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