Itolizumab in Psoriasis.
Ontology highlight
ABSTRACT:
SUBMITTER: Srivastava A
PROVIDER: S-EPMC5527725 | biostudies-other | 2017 Jul-Aug
REPOSITORIES: biostudies-other
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Project description:Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life.
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Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.
2014-10-30 | PXD001387 | Pride
Project description:Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations. Plaque psoriasis, which is the most common manifestation of psoriasis, is located on one end of the spectrum, dominated by adaptive immune responses, whereas the rarer pustular psoriasis lies on the opposite end, dominated by innate and autoinflammatory immune responses. In recent years, genetic studies have identified six genetic variants that predispose to pustular psoriasis, and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis. In this review, we discuss the presentation and clinical subtypes of pustular psoriasis, contribution of genetic predisposing variants, critical role of the IL-36 family of cytokines in disease pathophysiology, and treatment perspectives for pustular psoriasis. We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.
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Project description:Levels of anxiety and depression in twenty five patients with psoriasis were compared with anxiety and depression levels in equal number of age and sex matched normal controls, patients with nonpsychosomatic medical illnesses, and patients with neuroses. Sinha's anxiety scale and Hamilton's depression rating scale were used to measure anxiety and depression respectively. Analysis revealed that patients with psoriasis were significantly more anxious and depressed as compared to normal subjects and hospitalized patients with medical illnesses. Psoriatics were significantly less anxious and depressed than neurotics. Five patients with psoriasis were dependent on alcohol. Therapeutic implications of these findings are discussed.
| S-EPMC5530260 | biostudies-other
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| S-EPMC10407342 | biostudies-literature
Project description:Importance:Children with psoriasis are at increased risk for comorbidities. Many children with psoriasis are also overweight or obese; it is unknown whether the increased risk of comorbidities in these children is independent of obesity. Objective:To determine the risk of elevated lipid levels (hyperlipidemia/hypertriglyceridemia), hypertension, metabolic syndrome, polycystic ovarian syndrome, diabetes, nonalcoholic liver disease, and elevated liver enzyme levels in children with and without psoriasis, after accounting for obesity. Design, Setting, and Participants:This was a retrospective cohort study of claims data from Optum Laboratories Data Warehouse (includes 150 million privately insured and Medicare enrollees). A cohort of 29 957 children with psoriasis (affected children) and an age-, sex-, and race-matched comparator cohort of 29 957 children without psoriasis were identified and divided into 4 groups: (1) nonobese, without psoriasis (reference cohort); (2) nonobese, with psoriasis; (3) obese, without psoriasis; and (4) obese, with psoriasis. Main Outcomes and Measures:Risk of developing comorbidities (Cox proportional hazards regression). Results:The overall mean (SD) age of those included in the cohort was 12.0 (4.4) years, and 16 034 (53.5%) were girls. At baseline, more affected children were obese (862 [2.9%] vs 463 [1.5%]; P < .001 for all comparisons). Children with psoriasis were significantly more likely to develop each of the comorbidities than those without psoriasis (P < .01). Obesity was a strong risk factor for development of each comorbidity, even in those without psoriasis (hazard ratios [HRs] ranging from 2.26 to 18.11). The risk of comorbidities was 40% to 75% higher among nonobese children with vs without psoriasis: elevated lipid levels (HR, 1.42; 95% CI, 1.25-1.62), hypertension (HR, 1.64; 95% CI, 1.40-1.93), diabetes (HR, 1.58; 95% CI, 1.27-1.95), metabolic syndrome (HR, 1.62; 95% CI, 1.13-2.33), polycystic ovarian syndrome (HR, 1.49; 95% CI, 1.18-1.88), nonalcoholic liver disease (HR, 1.76; 95% CI, 1.16-2.65), and elevated liver enzyme levels (HR, 1.46; 95% CI, 1.27-1.67). Except for hypertension (P = .03), no significant interaction occurred between psoriasis and obesity on the risk of comorbidities. Conclusions and Relevance:Children with psoriasis are at greater risk of developing obesity, hyperlipidemia, hypertension, diabetes, metabolic syndrome, polycystic ovarian syndrome, nonalcoholic liver disease, and elevated liver function enzyme levels than children without psoriasis. While psoriasis is a small independent risk factor for the development of these comorbidities, obesity is a much stronger contributor to comorbidity development in children with psoriasis.
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Project description:The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-?, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases.
| S-EPMC4229247 | biostudies-literature
Project description:Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.
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Project description:Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 (AIM2), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.
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