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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/28634654/improvement-in-latent-variable-indirect-response-modeling-of-multiple-categorical-clinical-endpoints-application-to-modeling-of-guselkumab-treatment-effects-in-psoriatic-patients
#1
Chuanpu Hu, Bruce Randazzo, Amarnath Sharma, Honghui Zhou
Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23...
June 20, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28629323/fetal-death-in-utero-and-miscarriage-in-a-patient-with-crohn-s-disease-under-therapy-with-ustekinumab-case-report-and-review-of-the-literature
#2
C Venturin, S Nancey, P Danion, M Uzzan, M Chauvenet, C Bergoin, X Roblin, B Flourié, G Boschetti
BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage...
June 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28617942/withasteroid-b-from-d-metel-l-regulates-immune-responses-by-modulating-the-jak-stat-pathway-and-the-il-17-ror%C3%AE-t-il-10-foxp3-ratio
#3
Yang Su, Qiuhong Wang, Bingyou Yang, Lun Wu, Genhong Cheng, Haixue Kuang
Datura metel L. is a medicinal herb that contains withasteroids and has a wide range of biological activities. We isolated 7 withasteroids from the flowers of D. metel L(1) . and examined their ability to inhibit immune responses in vitro and in vivo. Among the withasteroids, B2(2) exhibited the strongest inhibitory effect on immune responses comparing B2 with other isolated compounds from D. metel L., including suppressing the differentiation of CD4(+3) T cells by inhibiting the expression and production of T cell lineage-specific master regulators and cytokines and directly suppressing the cytokine-induced JAK/STAT(4) signaling pathways...
June 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28602508/cyr61-ccn1-induces-ccl20-production-by-keratinocyte-via-activating-p38-and-jnk-ap-1-pathway-in-psoriasis
#4
Huidan Li, Haichuan Li, Rongfen Huo, Pinru Wu, Zhengyu Shen, Hui Xu, Baihua Shen, Ningli Li
BACKGROUND: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood. OBJECTIVE: In this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte. METHODS AND RESULTS: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion...
June 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28592369/preliminary-study-of-histamine-h4-receptor-expressed-on-human-cd4-t-cells-and-its-immunomodulatory-potency-in-the-il-17-pathway-of-psoriasis
#5
Song Hee Han, Min Seok Hur, Min Jung Kim, Bo Mi Kim, Kyoung Woon Kim, Hae Rim Kim, Yong Beom Choe, Kyu Joong Ahn, Yang Won Lee
BACKGROUND: Previous studies have shown the expression of histamine H4 receptor (H4R) on CD4(+) T cells, especially human CD4(+) Th2-polarized T cells. OBJECTIVE: This study aimed to investigate the role of H4R on these effector T cells in psoriasis. METHODS: We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4(+) T cells...
May 29, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28570274/tristetraprolin-expression-by-keratinocytes-controls-local-and-systemic-inflammation
#6
Mathieu Andrianne, Assiya Assabban, Caroline La, Denis Mogilenko, Delphine Staumont Salle, Sébastien Fleury, Gilles Doumont, Gaëtan Van Simaeys, Sergei A Nedospasov, Perry J Blackshear, David Dombrowicz, Stanislas Goriely, Laurye Van Maele
Tristetraprolin (TTP, encoded by the Zfp36 gene) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL‑23 by myeloid cells, such as macrophages or DCs. Here, we generated mice with conditional deletion of TTP in keratinocytes (Zfp36fl/flK14-Cre mice, referred to herein as Zfp36ΔEP mice)...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28547750/management-of-long-term-therapy-with-biological-drugs-in-psoriatic-patients-with-latent-tuberculosis-infection-in-real-life-setting
#7
Andrea Conti, Stefano Piaserico, Paolo Gisondi, Giulia Odorici, Giovanna Galdo, Claudia Lasagni, Giovanni Pellacani
Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long-term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate-to-severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti-TNF-α and/or anti IL 12, 23 and/or anti-CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X-ray suggestive, without clinical, or microbiological evidence of active disease...
May 26, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28542874/comparison-of-ixekizumab-with-ustekinumab-in-moderate-to-severe-psoriasis-24-week-results-from-ixora-s-a-phase-3-study
#8
K Reich, A Pinter, J P Lacour, C Ferrandiz, G Micali, L E French, M Lomaga, Y Dutronc, C Henneges, S Wilhelm, S Hartz, C Paul
BACKGROUND: The interleukin (IL)-23/IL-17 axis has been shown critical in the pathogenesis of psoriasis. OBJECTIVES: To present the primary endpoint (Week 12) and safety/efficacy data up to Week 24 from a head-to-head trial (IXORA-S) of the IL-17A inhibitor, ixekizumab (IXE), vs. the IL-12/23 inhibitor ustekinumab (UST). METHODS: Randomised patients received IXE (160-mg starting dose, then 80 mg every two weeks for 12 weeks, then 80 mg every four weeks, N=136) or UST (45 mg/90 mg weight-based dosing per label, N=166)...
May 19, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28532819/il-23-th17-targeted-therapies-in-sapho-syndrome-a-case-series
#9
Daniel Wendling, François Aubin, Frank Verhoeven, Clément Prati
SAPHO syndrome is a rare entity with skin and rheumatologic inflammatory presentation. The treatment is not standardized, and in case of inadequate response to anti inflammatory drugs, the use of anti TNF or anti IL-1 biologic treatments has been reported. The IL-23/Th17 axis may be involved in SAPHO syndrome. We report the results of six courses of IL-23 and IL-17 targeted therapies (3 ustekinumab and 3 secukinumab) in patients with SAPHO syndrome unresponsive to previous treatments (csDMARDs and bDMARDs)...
May 19, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28499587/the-phosphodiesterase-4-inhibitor-apremilast-inhibits-th1-but-promotes-th17-responses-induced-by-6-sulfo-lacnac-slan-dendritic-cells
#10
Stephanie Oehrl, Hridayesh Prakash, Annette Ebling, Nina Trenkler, Priscila Wölbing, Anja Kunze, Thomas Döbel, Marc Schmitz, Alexander Enk, Knut Schäkel
BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs...
April 20, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28489479/biologics-and-dermatology-life-quality-index-dlqi-in-the-australasian-psoriasis-population
#11
Diana Norris, Louise Photiou, Mark Tacey, Con Dolianitis, George Varigos, Peter Foley, Chris Baker
BACKGROUND/OBJECTIVES: Psoriasis is a chronic condition that may require long-term treatment for disease control. This analysis utilises data from the Australasian Psoriasis Registry with particular attention to the impact of biologic therapy on DLQI, and the differences between the biologics in terms of DLQI score change. METHODS: A retrospective review of patients enrolled in the Australasian Psoriasis Registry from April 2008 to August 2016 was conducted. All subjects from the registry that had DLQI and Psoriasis Assessment Severity Index (PASI) scores recorded at a baseline timepoint of treatment commencement, in addition to week 12 and 24 post commencement were included in the study...
May 10, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28469254/immune-checkpoint-protein-vista-critically-regulates-the-il-23-il-17-inflammatory-axis
#12
Na Li, Wenwen Xu, Ying Yuan, Natarajan Ayithan, Yasutomo Imai, Xuesong Wu, Halli Miller, Michael Olson, Yunfeng Feng, Yina H Huang, Mary Jo Turk, Samuel T Hwang, Subramaniam Malarkannan, Li Wang
V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an inhibitory immune-checkpoint molecule that suppresses CD4(+) and CD8(+) T cell activation when expressed on antigen-presenting cells. Vsir (-/-) mice developed loss of peripheral tolerance and multi-organ chronic inflammatory phenotypes. Vsir (-/-) CD4(+) and CD8(+) T cells were hyper-responsive towards self- and foreign antigens. Whether or not VISTA regulates innate immunity is unknown. Using a murine model of psoriasis induced by TLR7 agonist imiquimod (IMQ), we show that VISTA deficiency exacerbated psoriasiform inflammation...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464025/pams-ameliorates-the-imiquimod-induced-psoriasis-like-skin-disease-in-mice-by-inhibition-of-translocation-of-nf-%C3%AE%C2%BAb-and-production-of-inflammatory-cytokines
#13
Rongkun Dou, Zongying Liu, Xue Yuan, Danzhou Xiangfei, Ruixue Bai, Zhenfei Bi, Piao Yang, Yalan Yang, Yinsong Dong, Wei Su, Diqiang Li, Canquan Mao
Psoriasis is a chronic and persistent inflammatory skin disease seriously affecting the quality of human life. In this study, we reported an ancient formula of Chinese folk medicine, the natural plant antimicrobial solution (PAMs) for its anti-inflammatory effects and proposed the primary mechanisms on inhibiting the inflammatory response in TNF-α/IFN-γ-induced HaCaT cells and imiquimod-induced psoriasis-like skin disease mouse model. Two main functional components of hydroxysafflor Yellow A and allantoin in PAMs were quantified by HPLC to be 94...
2017: PloS One
https://www.readbyqxmd.com/read/28461763/emerging-targeted-therapies-for-plaque-psoriasis-impact-of-ixekizumab
#14
REVIEW
Tiana Kazemi, Benjamin Farahnik, John Koo, Kourosh Beroukhim
BACKGROUND: Recent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17) in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA)-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis. METHODS: We reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28461524/basic-and-translational-science-a-report-from-the-grappa-2016-annual-meeting
#15
James G Krueger, Bruce Kirkham, Christopher T Ritchlin
Rapid advances in effective treatments for psoriasis and psoriatic arthritis (PsA) have emerged from improved understanding of cell subsets and critical mediators that promote tissue inflammation and destruction. More specifically, increased knowledge of innate immunity and the important involvement of cytokines in the interleukin (IL)-23-IL-17 axis as key mediators of psoriatic plaque and joint inflammation in both psoriasis and PsA have led to new theories of immunopathogenesis. Herein we summarize recent discussions on IL-17-related pathways and their relationship to psoriasis and PsA...
May 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28461105/il-10-producing-bregs-are-impaired-in-psoriatic-arthritis-and-psoriasis-and-inversely-correlate-with-il-17-and-ifn%C3%AE-producing-t-cells
#16
Athanasios Mavropoulos, Areti Varna, Efterpi Zafiriou, Christos Liaskos, Ioannis Alexiou, Aggeliki Roussaki-Schulze, Marianna Vlychou, Christina Katsiari, Dimitrios P Bogdanos, Lazaros I Sakkas
Our aim was to study CD19(+)CD27(+)CD24(high) memory and CD19(+)CD24(high)CD38(high) transitional and IL-10+Breg cells, known to inhibit Th1 and Th17 cells in experimental arthritis, in psoriatic arthritis (PsA) and psoriasis (Ps). Peripheral blood Breg cells from 60 patients with PsA, 50 patients with Ps and 23 healthy controls were analyzed by flow cytometry. IL-17A-producing CD3(+) T cells and IFNγ-producing CD3(+) T cells and activation of p38 MAPK and STAT3 were also studied. CD19(+)CD27(+)CD24(high) and CD19(+)CD24(high)CD38(high) Breg cells were decreased in PsA and Ps...
April 28, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28460549/pharmacokinetic-drug-evaluation-of-brodalumab-for-the-treatment-of-psoriasis
#17
REVIEW
M Galluzzo, M Talamonti, S D'adamio, L Bianchi
Psoriasis is now understood to also be under the driving influence of the IL-17/IL-23 axis, and the medical breakthrough of novel IL-17 inhibitor medications signals a paradigm shift in the way psoriatic patients are managed medically. Brodalumab, a fully human Chinese hamster ovary cell-derived immunoglobulin G2 (IgG2) anti-IL-17RA monoclonal antibody, is currently the most-developed treatment that binds to the IL-17RA. The authors review and provide updates of efficacy and safety by several studies on brodalumab...
June 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28444425/pharmacogenetic-markers-to-predict-the-clinical-response-to-methotrexate-in-south-indian-tamil-patients-with-psoriasis
#18
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/28441904/the-safety-of-ustekinumab-for-the-treatment-of-psoriatic-arthritis
#19
REVIEW
A López-Ferrer, A Laiz, L Puig
The cytokines interleukin (IL)-12 and IL-23 have been involved in the pathogenesis of psoriasis and psoriatic arthritis. Ustekinumab is a fully human monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 binding to their receptors, blocking the T1 and T17 inflammatory pathways. Ustekinumab has been evaluated for the treatment of various chronic immune mediated diseases including psoriasis and psoriatic arthritis (PsA). Most of the data regarding the safety of ustekinumab come from the experience treating patients with psoriasis, but clinical trials have demonstrated its efficacy and safety in the treatment of both diseases...
June 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28431948/serum-peptides-as-putative-modulators-of-inflammation-in-psoriasis
#20
Tetsuhiko Matsuura, Masaaki Sato, Kouhei Nagai, Toshiyuki Sato, Mitsumi Arito, Kazuki Omoteyama, Naoya Suematsu, Kazuki Okamoto, Tomohiro Kato, Yoshinao Soma, Manae S Kurokawa
BACKGROUND: Psoriasis is a refractory inflammatory disease, however, its pathophysiology is still not fully understood. OBJECTIVE: We tried to identify novel serum peptides associated with the pathophysiology of psoriasis. METHODS: Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23 healthy control (HC) subjects were analyzed by mass spectrometry...
March 27, 2017: Journal of Dermatological Science
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