Multi-omics approach identifies PI3 as a biomarker for disease severity and hyper-keratinization in psoriasis
Jingwen DengEmmerik F A LeijtenYongzhan ZhuMichel Olde NordkampShuyan YeJuliëtte PouwWeiyang TaoDeepak BalakGuangjuan ZhengTimothy R. D. J. RadstakeLing HanJosé A. M. BorghansChuanjian LuAridaman Pandit
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BackgroundPsoriasis is an immune-mediated inflammatory skin disease. Psoriasis severity evaluation is important for clinicians in the assessment of disease severity and subsequent clinical decision making. However, no objective biomarker is available for accurately evaluating disease severity in psoriasis.ObjectiveTo define and compare biomarkers of disease severity and progression in psoriatic skin.MethodsWe performed proteome profiling to study the proteins circulating in the serum from patients with psoriasis, psoriatic arthritis and ankylosing spondylitis, and transcriptome sequencing to investigate the gene expression in skin from the same cohort. We then used machine learning approaches to evaluate different biomarker candidates across several independent cohorts. In order to reveal the cell-type specificity of different biomarkers, we also analyzed a single-cell dataset of skin samples. In-situ staining was applied for the validation of biomarker expression.ResultsWe identified that the peptidase inhibitor 3 (PI3) was significantly correlated with the corresponding local skin gene expression, and was associated with disease severity. We applied machine learning methods to confirm that PI3 was an effective psoriasis classifier, Finally, we validated PI3 as psoriasis biomarker using in-situ staining and public datasets. Single-cell data and in-situ staining indicated that PI3 was specifically highly expressed in keratinocytes from psoriatic lesions.ConclusionOur results suggest that PI3 may be a psoriasis-specific biomarker for disease severity and hyper-keratinization.Keywords:
Omics
Drug ingestion may play an important role in the induction and exacerbation of psoriasis. Drugs may directly induce the occurrence of psoriasis in susceptible individuals, or cause the recurrence or exacerbation of preexisting psoriasis. In view of their relationship with psoriasis, drugs can be classified as follows: drugs that are definitely able to induce or exacerbate psoriasis (e.g., lithium), and drugs that are possible to induce or exacerbate psoriasis (e.g., interferon). Clinical and histological studies on drug-induced or-exacerbated psoriasis are helpful to investigate into the pathogenesis of psoriasis. Further studies are still needed for drugs that are possible to induce or exacerbate psoriasis, which may be of great importance for the prevention of psoriasis in susceptible individuals.
Key words:
Psoriasis; Pharmaceutical preparations; Lithium compounds; Antimalarials; Biological agents; Provoke; Exacerbate
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Objective To Investigate whether the PDEs activities is abnormal or not in psoriasis patients by detecting the PDEs activities of both psoriasis patients and healthy controls, and explore the potential role of PDEs activities changes in the pathogenesis of psoriasis. Methods PDEs activities were detected by using high performance liquid chromatography(HPLC) in 50 patients with psoriasis and 60 healthy controls. Results The PDEs activities is 10.40%±3.54% in psoriasis patients,and 8.60%±2.25% in the healthy controls. The PDEs activities in patients with psoriasis is significant higher than that in the controls (P0.05). Conclusions The PDEs activities may be a risk factor for psoriasis.
Pathogenesis
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Psoriasis is a chronic, immune-mediated, inflammatory disorder characterized by erythema, redness, thickening, and scaling of the skin. Psoriasis is caused by the accelerated keratinocyte cell proliferation and dysregulation of the immune system. The cause of psoriasis is unknown, but it can be a genetic component. Several factors are thought to aggravate psoriasis. These include stress, excessive alcohol consumption, and smoking. The concept of the pathogenesis of psoriasis is based on the proliferation and differentiation of keratinocytes, recent studies have proved that the dysregulation of the immune system plays a critical role in the development of psoriasis. Immune cells release T cells, keratinocytes, neutrophils, and the cytokines, have a specific interaction with each other that is the core mechanism of the development of psoriasis. Trigger factors of psoriasis is also genetic, environmental and behavioral factors. The prevalence of psoriasis is estimated to range from 0.91% to 8.5% worldwide in adults. Clinically, psoriasis vulgaris is the most common subtype of psoriasis and affects approximately 90% of patients.
Immune Dysregulation
Pathogenesis
Erythema
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Sun Exposure
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【Objectives】 To test the expression levels of soluble CD147(sCD147) in plasma of psoriasis vulgaris(PV) patients and normal controls. Describe disease severity of PV with psoriasis lesion degree score(PASI) and analyze the correlation between the expression levels of sCD147 in psoriasis patients and disease severity. To test the expression levels of sCD147 in plasma of different subtypes of psoriasis patients, and study the roles of sCD147 play in the psoriasis classification. 【Methods】 Detect the expression levels of sCD147 in 74 PV patients and 41 normal controls by enzyme-linked immunosorbent assay(ELISA). Analyze the correlation between sCD147 expression levels and PASI score. Detect the expression levels of sCD147 of plasma in 10 patients with psoriasis pustulose(PP), 12 patients with arthritis psoriasis(PsA) and 7 patients with psoriasis erythrodermic(PE). Statistical analyze the difference of sCD147 expression levels in patients with different subtypes of psoriasis. 【Results】 The sCD147 expression levels in plasma of PV patients were significantly higher than those in normal controls(Ctrl)(P 0.01). Statistical analysis showed that there was no correlation between sCD147 expression level and PASI score(r =0.123, P =0.298). There was significant difference of sCD147 expression levels in different subtypes of psoriasis patients(PV PP PsA PE)(P 0.001). 【Conclusion】The expression levels of sCD147 is significantly increased in psoriasis patients. There is statistical significance of sCD147 expression levels in four subtypes of psoriasis. Thus, sCD147 may become a new target for psoriasis drug treatment.
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Acute generalized exanthematous pustulosis (AGEP) is a rare pustular severe cutaneous adverse reaction. Differentiating between AGEP and pustular psoriasis may represent a diagnostic challenge. We sought to evaluate the prevalence of comorbidities in a series of patients with AGEP compared to a series of patients with psoriasis vulgaris and to a series of patients with drug-related psoriasis.Medical records of 14 patients with AGEP, 33 patients with psoriasis vulgaris, and 18 patients with drug-related psoriasis were reviewed. The presence of comorbidities was recorded, and a comparative analysis was performed.A personal history of psoriasis was present in 4 (28%) patients with AGEP compared to 12 (66%) patients with drug-related psoriasis (Pv=0.03). The prevalence of psoriasis-related morbidities was significantly lower in the AGEP group compared to the psoriasis group and to the drug-related psoriasis group (Pv<0.01, 0.05, respectively). Each of the psoriasis-related morbidities had significantly lower prevalence in the AGEP group compared to the psoriasis group and to the drug-related psoriasis group (Pv<0.01).In conclusion, differences between AGEP, psoriasis vulgaris, and drug-related psoriasis regarding the prevalence of psoriasis-related morbidities may assist differentiation in borderline cases.
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A large number of different measurements is used to assess severity of psoriasis and treatment efficacy of this entity. The best known and most frequently used is the Psoriasis Area and Severity Index . But there are many other measurements, which have both advantages and disadvantages. Below we have characterized the most commonly used psoriasis scales: Body Surface Area , Physician’s Global Assessment , Lattice System Physician’s Global Assessment , Simplified Psoriasis Index , Salford Psoriasis Index , Self-Administered Psoriasis Area and Severity Index , Simplified Psoriasis Area Severity Index , Psoriasis Assessment Severity Score , Psoriasis Log-based Area and Severity Index , Psoriasis Exact Area and Severity Index , Copenhagen Psoriasis Severity Index , National Psoriasis Foundation Psoriasis Score , Nail Psoriasis Severity Index , Dermatology Life Quality Index . There has been no single ideal instrument yet developed to assess severity of psoriasis, which is free of limitations in use. Therefore, further studies on the optimization and proper validation of tools for assessing the severity of psoriasis are needed.
Body surface area
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This chapter contains sections titled: Introduction History of psoriasis Who gets psoriasis? Biology of psoriasis Comorbidities associated with psoriasis Clinical variants of psoriasis Physical symptoms that accompany psoriasis Trigger factors in psoriasis Treatments for psoriasis Measuring quality of life Conclusion References
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Interleukin-20 (IL-20) is suggested as a new target in psoriasis treatment. It was first described in 2001, and the potential role of this cytokine in psoriasis was suggested because mice which were over-expressing IL-20 developed a psoriasis-like phenotype of the skin. Subsequently, IL-20 expression levels were found to be increased in psoriasis skin, and it was observed that these levels normalized upon psoriasis treatment. In the psoriasis xenograft transplantation model, administration of IL-20 to non-lesional psoriasis skin transplanted onto immune-deficient mice demonstrated that IL-20 was involved in the psoriasis induction. More interestingly, improvement of psoriasis was induced by blocking IL-20 signaling.
Interleukin 22
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Psoriasis treatment using psorinum autonosode is discussed. 50 years old male has been suffering from psoriasis for over three years with multiple psoriasis patches on his hands and feet. Psorinum autonosode was prepared from psoriasis scales using Korsakov’s method and taken twice a day. In about a month of taking the autonosode, the psoriasis patches disappeared completely and have not come back for over two years.
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