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Psoriatic arthritis and gene therapy

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
Maria I Ramos, Marcel B M Teunissen, Boy Helder, Saida Aarrass, Maria J H de Hair, Arno W van Kuijk, Danielle M Gerlag, Paul P Tak, Maria C Lebre
OBJECTIVES: We aimed to investigate the early changes in expression of C-type lectin domain family 9, member A (CLEC9A), a C-type lectin that is specifically expressed by the CD141(+) dendritic cell subset that is involved in cross-presentation to CD8(+) T cells, by evaluating gene and/or protein expression in three different compartments [skin, synovial tissue (ST) and serum] after short-term adalimumab treatment in PsA patients compared with placebo. METHODS: Patients with active PsA and psoriasis were randomized to receive adalimumab or placebo for 4 weeks...
September 2016: Rheumatology
Caroline Aalbers, Danielle Gerlag, Koen Vos, Margriet Vervoordeldonk, Robert Landewé, Paul Peter Tak
OBJECTIVE: There is an increased interest in developing gene therapy approaches for local delivery of therapeutic genes in patients with arthritis. Intra-articular (i.a.) gene delivery, using an adeno-associated virus encoding a TNF soluble receptor, resulted in reduced paw swelling in an arthritis animal model, but i.a. treatment with a similar vector did not induce robust clinical improvement in patients. It is unclear whether this can be explained by for instance insufficient transduction efficiency or the fact that TNF is not a good therapeutic target for i...
October 2015: Joint, Bone, Spine: Revue du Rhumatisme
Meghna Jani, Anne Barton, Pauline Ho
TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed treatments in psoriatic arthritis. A large proportion of patients do not respond to these medications, although unfortunately clinically useful biomarkers that predict future response are currently lacking. Several candidate gene polymorphisms have been associated with responses to biologic therapies and nbDMARDs; however, replication and validation of these variants in large prospective psoriatic arthritis cohorts are required before translating these to clinical practice...
July 2015: Current Rheumatology Reports
C De Simone, M Farina, A Maiorino, C Fanali, F Perino, A Flamini, G Caldarola, A Sgambato
BACKGROUND: Genetic factors might have a role for lack of therapeutic response to anti-TNF-alpha agents, as previously suggested in patients with rheumatoid arthritis and inflammatory bowel disease. OBJECTIVES: We evaluated the role of the main TNF-alpha polymorphisms (-238G>A, -308G>A, -857C>T) in predicting the response to etanercept, an anti-TNF-alpha fusion protein. MATERIAL AND METHODS: Genomic DNA was extracted from buccal epithelial cells in a series of 97 psoriatic patients who received etanercept for at least 3 months...
September 2015: Journal of the European Academy of Dermatology and Venereology: JEADV
M García-Carrasco, C Mendoza-Pinto, S Macias Díaz, M Vera-Recabarren, L Vázquez de Lara, S Méndez Martínez, P Soto-Santillán, R González-Ramírez, A Ruiz-Arguelles
P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified...
July 2015: Autoimmunity Reviews
Jennifer Belasco, James S Louie, Nicholas Gulati, Nathan Wei, Kristine Nograles, Judilyn Fuentes-Duculan, Hiroshi Mitsui, Mayte Suárez-Fariñas, James G Krueger
OBJECTIVE: To our knowledge, there is no broad genomic analysis comparing skin and synovium in psoriatic arthritis (PsA). Also, there is little understanding of the relative levels of cytokines and chemokines in skin and synovium. The purpose of this study was to better define inflammatory pathways in paired lesional skin and affected synovial tissue in patients with PsA. METHODS: We conducted a comprehensive analysis of cytokine and chemokine activation and genes representative of the inflammatory processes in PsA...
April 2015: Arthritis & Rheumatology
Alexander Rosenberg, Hongtao Fan, Yahui G Chiu, Rebecca Bolce, Darren Tabechian, Rick Barrett, Sharon Moorehead, Frédéric Baribaud, Hao Liu, Nancy Peffer, David Shealy, Edward M Schwarz, Christopher T Ritchlin
OBJECTIVE: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases. METHODS: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment...
2014: PloS One
Nataliya Yeremenko, Jacqueline E Paramarta, Dominique Baeten
PURPOSE OF REVIEW: Various novel therapies for spondyloarthritis (SpA) are currently under development. In this review, we discuss the scientific rational to target the interleukin (IL)-23/IL-17 axis in SpA and give an overview of the proof-of-concept trials with drugs directed towards this axis. RECENT FINDINGS: Cumulative evidence from genetics (e.g. the strong genetic association with the IL-23 receptor gene), in-vitro models (e.g. the increased IL-23 production upon HLA-B27 misfolding), human expression studies (e...
July 2014: Current Opinion in Rheumatology
Izabela Kokot, Lilla Pawlik-Sobecka, Sylwia Płaczkowska, Agnieszka Piwowar
Prolactin (PRL) is a hormone synthesized and secreted by lactotroph cells in the anterior pituitary gland. There is also extrapituitary hormone secretion by many cells, including cells of the immune system. In physiological conditions PRL is responsible for lactogenesis and other processes associated with it. PRL plays a significant role during the immune response as a cytokine, affecting proliferation and differentiation of many immune system cells. The biological effect of the hormone depends on binding with the specific prolactin receptor PRL-R, and activation of the transcription factors of targeted genes...
2013: Postȩpy Higieny i Medycyny Doświadczalnej
Caitriona Ryan, Neil J Korman, Joel M Gelfand, Henry W Lim, Craig A Elmets, Steven R Feldman, Alice B Gottlieb, John Y M Koo, Mark Lebwohl, Craig L Leonardi, Abby S Van Voorhees, Reva Bhushan, Alan Menter
Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits...
January 2014: Journal of the American Academy of Dermatology
W H Boehncke, B Kirby, O Fitzgerald, P C M van de Kerkhof
Psoriatic arthritis (PsA) is a spondyloarthritis with a comorbid association with psoriasis. Without appropriate treatment it can be progressive, severe, deforming and destructive. It has long been recognized that subsets of PsA patients exist, characterized by different patterns of joint involvement. Associations between development of PsA and certain human leukocyte antigens (HLA) have been established. Evidence now suggests that progression of PsA is also genetically determined. The presence of one allele (HLA-B*27) has been associated with a distinct phenotype characterized by early joint involvement, whereas development of musculoskeletal symptoms is much slower in patients with another allele, C*06...
March 2014: Journal of the European Academy of Dermatology and Venereology: JEADV
Qingping Yao
OBJECTIVES: To systematically review literature about the structure and function of nucleotide-binding oligomerization domain containing 2 (NOD2) and its disease association. METHODS: The English literature was searched using keywords "NOD2" and "disease". Relevant original and review articles were reviewed. RESULTS: NOD2 is an intracellular protein and shares similar molecular structure with NOD1, pyrin, and cryopyrin. There are more than 100 NOD2 gene mutations, some of which have been linked to diseases such as Crohn disease, Blau syndrome, and NOD2-associated autoinflammatory disease (NAID)...
August 2013: Seminars in Arthritis and Rheumatism
R Prieto-Pérez, T Cabaleiro, E Daudén, F Abad-Santos
Psoriasis (Ps) is a chronic inflammatory disease with an important genetic component. It shares pathophysiological mechanisms with other autoimmune diseases such as psoriatic arthritis (PsA), rheumatoid arthritis (RA) and Crohn's disease (CD). These conditions can be treated using biological drugs such as infliximab, adalimumab and etanercept, which selectively block the proinflammatory cytokine tumor necrosis factor (TNF)-α. Although these agents have greatly improved the prognosis of Ps, PsA, RA and CD, they do not cure the disease and are expensive; in addition, significant proportions of patients do not respond or develop serious adverse effects...
August 2013: Pharmacogenomics Journal
Peter Lloyd, Caitriona Ryan, Alan Menter
Psoriatic arthritis is a debilitating condition, which affects approximately one-quarter of psoriasis patients. Recent findings have furthered our understanding of the complex pathophysiology of PsA. There have been major advances in the identification of genes associated with joint involvement but not with cutaneous disease alone. The elucidation of key immunologic pathways has allowed the development of novel targeted therapies that are in the research pipeline. Currently, good screening tests and biomarkers to diagnose early PsA and to guide therapy are limited...
2012: Arthritis
A Scardapane, L Breda, M Lucantoni, F Chiarelli
Whether tumor necrosis factor alpha (TNF-α) gene polymorphisms (SNPs) influence disease susceptibility and treatment of patients with juvenile idiopathic arthritis (JIA) is presently uncertain. TNF-α is one of the most important cytokine involved in JIA pathogenesis. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only a very small minority have proven functional consequences and have been associated with susceptibility to JIA. An association between some TNF-α SNPs and adult rheumatoid arthritis (RA) susceptibility, severity and clinical response to anti-TNF-α treatment has been reported...
2012: International Journal of Rheumatology
(no author information available yet)
OBJECTIVE: The purpose of this evidence based analysis was to determine the effectiveness and safety of ultraviolet phototherapy for moderate-to-severe plaque psoriasis. RESEARCH QUESTIONS: The specific research questions for the evidence review were as follows: What is the safety of ultraviolet phototherapy for moderate-to-severe plaque psoriasis?What is the effectiveness of ultraviolet phototherapy for moderate-to-severe plaque psoriasis? CLINICAL NEED: TARGET POPULATION AND CONDITION Psoriasis is a common chronic, systemic inflammatory disease affecting the skin, nails and occasionally the joints and has a lifelong waning and waxing course...
2009: Ontario Health Technology Assessment Series
María José Morales-Lara, Juan D Cañete, Daniel Torres-Moreno, María Victoria Hernández, Francisco Pedrero, Raquel Celis, María Sergia García-Simón, Pablo Conesa-Zamora
OBJECTIVES: As the role of polymorphisms in death receptors (DRs) such as Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Tumor Necrosis Factor Receptor 1A (TNF-R1A) on the response to anti-TNF therapy remains unknown, we evaluated the association between TRAILR1 and TNFR1A gene polymorphisms (rs20575/C626G and rs767455/G36A) and the pharmacogenetics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with TNFα blockers. METHODS: One hundred and forty-five patients (90 RA and 55 PsA) treated with anti-TNFα therapy (RA: 75 infliximab, 8 etanercept, 7 adalimumab...
December 2012: Joint, Bone, Spine: Revue du Rhumatisme
Darren D O'Rielly, Proton Rahman
Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, has a wide spectrum of disease severity. The clinical heterogeneity in PsA probably reflects substantial genetic heterogeneity. In recent years, many genes that contribute to the pathogenesis of psoriasis and PsA have been identified, especially in Western cohorts. Emerging evidence from functional studies of candidate genes identified by genome-wide association studies is suggestive of an integrated, multi-tiered pathogenic model, comprising distinct signaling networks that affect skin barrier function, innate immune responses (involving NFκB and interferon signaling), and adaptive immune responses (involving CD8(+) T cells and type 17 T-helper-cell signaling)...
December 2011: Nature Reviews. Rheumatology
H L Hébert, F R Ali, J Bowes, C E M Griffiths, A Barton, R B Warren
The era of genome-wide association studies has revolutionized the search for genetic susceptibility loci in complex genetic conditions such as psoriasis. There are currently 16 loci with confirmed evidence for association with psoriasis susceptibility but there is the potential for more to be discovered as the genetic heritability of the disease has not yet been fully explained. Many of the associated loci overlap with those for psoriatic arthritis. In contrast to psoriasis susceptibility, few studies have been performed to identify predictors of drug response in psoriasis...
March 2012: British Journal of Dermatology
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