Biomarkers For Psoriasis Research Articles

Serum CRP, endoglin, E-selectin, and Tie-1 as biomarkers in psoriasis

Serum CRP, endoglin, E-selectin, and Tie-1 as biomarkers in psoriasis

Assessment and Clinical Relevance of Serum IL-19 Levels in Psoriasis and Atopic Dermatitis Using a Sensitive and Specific Novel Immunoassay

Because development of reliable biomarkers in psoriasis and atopic dermatitis has lagged behind therapeutic progress, we created a blood-based test to fill the void in objective methods available for dermatological assessments. Our novel interleukin-19 (IL-19) immunoassay was initially tested to determine concentrations of IL-19 serum levels, then correlated with the psoriasis activity and severity index (PASI) in psoriasis, and the eczema area and severity index (EASI) in atopic dermatitis. Not only was IL-19 increased in psoriasis and correlated to PASI, but ixekizumab administration led to rapid, sustained IL-19 decreases to normal levels, with decreases at 2-weeks correlating with PASI improvement at 16-weeks. IL-19 increased upon ixekizumab withdraw, prior to relapse, and decreased following re-treatment. In baricitinib- and etanercept-treated psoriasis patients, IL-19 decreases also correlated with improvement. Many patients with limited skin disease, including genital psoriasis and psoriatic arthritis patients, also had increased IL-19, which was reduced to normal levels upon ixekizumab treatment, correlating with PASI improvement. We also measured IL-19 in baricitinib-treated atopic dermatitis patients. In atopic dermatitis, IL-19 was significantly elevated, correlated with EASI scores, and decreased with skin improvement. Therefore, measurement of serum IL-19 provides clinicians with an objective disease-activity assessment tool for psoriasis and atopic dermatitis patients.

Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins.S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity.Trial Registration: DRKS 00014817.

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine.

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum.Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays.Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B).Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.

Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment

Background: In psoriasis, a common immune-mediated disease affecting 2–3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment. Objective: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis. Methods: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response. Results: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10–12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction. Conclusion: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis.

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N=73) were conducted, which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P<0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve=0.85, P<0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index scores (R=0.32, P=0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P=0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis.

Systems biomarkers in psoriasis: Integrative evaluation of computational and experimental data at transcript and protein levels

Psoriasis is a complex autoimmune disease with multiple genes and proteins being involved in its pathogenesis. Despite the efforts performed to understand mechanisms of psoriasis pathogenesis and to identify diagnostic and prognostic targets, disease-specific and effective biomarkers were still not available. This study is compiled regarding clinical validation of computationally proposed biomarkers at gene and protein expression levels through qRT-PCR and ELISA techniques using skin biopsies and blood plasma. We identified several gene and protein clusters as systems biomarkers and presented the importance of gender difference in psoriasis. A gene cluster comprising of PI3, IRF9, IFIT1 and NMI were found as positively correlated and differentially co-expressed for women, whereas SUB1 gene was also included in this cluster for men. The differential expressions of IRF9 and NMI in women and SUB1 in men were validated at gene expression level via qRT-PCR. At protein level, PI3 was abundance in disease states of both genders, whereas PC4 protein and WIF1 protein were significantly higher in healthy states than disease states of male group and female group, respectively. Regarding abundancy of PI3 and WIF1 proteins in women, and PI3 and PC4 in men may be assumed as systems biomarkers at protein level.

The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease.

Psoriasis is a physically, emotionally, and socially invalidating multifactorial disorder, with a significant impact on the patients' quality of life. Stress is one of the leading triggers for psoriasis and has been associated with disease onset and subsequent flare-ups, while the flare-ups by themselves often lead to psychological discomfort. The treatment of psoriasis is individualized, depending on the patients' measurable severity of illness, as well as the impact the skin condition has on patients' quality of life, as assessed by standardized questionnaires. The clinical scales used nowadays for measuring the severity of psoriasis are characterized by low reproducibility and high variability between examiners. Hence, there is a real need to identify objectively measurable biomarkers to standardize the assessment of the severity of psoriasis. We aim to review the pathophysiological mechanisms involved in psoriasis, focusing on the most critical advances in psoriasis biomarker discovery, pointing out those biomarkers which have also been studied in other stress-related conditions, thus emphasizing the relationship between psoriasis and stress.

Circular RNA Expression Profile and Analysis of Their Potential Function in Psoriasis

Background/Aims: Circular RNAs (circRNAs) are evolutionary conserved circular non-coding RNAs that play a role in several diseases by sequestering (sponging) microRNAs (miRNAs). However, their role in psoriasis remains unclear. In the present study, we investigated the expression of circRNAs and analyzed their potential functions in psoriasis. Methods: The SBC human ceRNA array V1.0 was used to analyze circRNA expression in psoriatic lesions and normal healthy skin tissues. Functional analyses were performed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Putative miRNA response elements (MREs) were identified using miRNA target prediction software. Six upregulated circRNAs were verified by quantitative real-time reverse transcription polymerase chain reaction in psoriatic lesions and healthy skin tissues. Results: A total of 4956 circRNAs (3016 upregulated and 1940 downregulated; fold change ≥2 and p< 0.05) were identified as differentially expressed in psoriasis. Furthermore, 4405 MREs were identified among the differentially expressed circRNAs. hsa_circ_0061012 was upregulated in psoriatic lesions compared with normal healthy skin tissues. The top five MREs of hsa_circ_0061012 were hsa-miR-7157-5p, hsa-miR-4769-3p, hsa-miR-6817-5p, hsa-miR-4310, and hsa-miR-6882-3p. GO analysis was carried out to investigate the biological functions enriched among the upregulated targets of five miRNAs in psoriasis. The GO analysis identified that most of top 30 of GO enrichment are related to psoriasis. Conclusion: hsa_circ_0061012 might be a candidate biomarker for psoriasis. The results provide a new perspective for a better understanding of ceRNA-mediated gene regulation in psoriasis, and provide a novel theoretical basis for further studies on the function of circRNA in psoriasis.

Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta-analysis.

PurposeTo evaluate the association of serum levels of adipokines and cytokines with psoriasis.Materials and MethodsA comprehensive literature search was performed in PubMed, ScienceDirect and Web of Science for the available relevant studies published before December 1, 2016. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs) with 95% confidence interval to combine the effect estimations. We also conducted stratified analysis, meta-regression analysis and sensitivity analysis.ResultsSixty-three studies containing 2876 psoriasis patients and 2237 healthy controls were included in this meta-analysis. The pooled serum levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-18, IL-22, chemerin, lipocalin-2, resistin, sE-selectin, fibrinogen and C3 were higher in psoriasis patients compared with healthy controls (all P < 0.05). In contrast, adiponectin levels were lower. Serum levels of IL-1β, IL-4, IL-10, IL-12, IL-17, IL-21, IL-23, visfatin and omentin were not significantly different between psoriasis patients and controls (all P > 0.05). However, increased serum levels of IL-17 correlated with psoriasis in men. For other biomarkers, age, gender and psoriasis area and severity index did not explain the differences in effect size between the studies.ConclusionsSerum levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-18, IL-22, chemerin, lipocalin-2, resistin, sE-selectin, fibrinogen, complement 3, and adiponectin correlate with psoriasis and can be used as potential biomarkers for psoriasis and response to the treatment. Future studies are needed to identify additional players involved in the pathogenesis of psoriasis and to fully decipher the underlying mechanism.

Precision assessment of label-free psoriasis biomarkers with ultra-broadband optoacoustic mesoscopy

Imaging plays a critical role in the diagnosis and assessment of dermatological conditions. However, optical or optoacoustic microscopy techniques are limited to visualizing superficial skin features owing to strong photon scattering, whereas ultrasound methods, which can probe deeper-seated tissue, lack the contrast to image pathophysiological mechanisms in detail. Here, we demonstrate that raster-scan optoacoustic mesoscopy (RSOM) implemented in ultra-broadband (10–180 MHz) detection mode bridges the depth capabilities of ultrasound and the resolution range and high contrast of optical methods in clinical dermatology. Using tomographic reconstruction and frequency equalization to represent low and high spatial-frequency components, we visualize skin morphology and vascular patterns in the dermis and sub-dermis of psoriasis patients, enabling quantification of inflammation and other biomarkers of psoriasis without the need for contrast agents. Implemented in a handheld device, we showcase how label-free biomarkers detected by RSOM correlate with clinical score. The method can also be extended to assess a larger spectrum of dermatological conditions. Ultra-broadband optoacoustic mesoscopy implemented in a handheld device enables the visualization of vascular patterns in the dermis and sub-dermis of psoriasis patients, and the quantification of inflammatory biomarkers of psoriasis.

Chitinase-3-Like Protein 1 (YKL-40) Is a New Biomarker of Inflammation in Psoriasis.

Purpose The evaluation of new inflammatory biomarkers in psoriasis could determine therapeutic decisions. Chitinase-3-like protein 1 (YKL-40) plays a role in inflammation. The study was undertaken to check whether YKL-40 is a reliable biomarker of inflammation in psoriasis. Materials and Methods 55 psoriatic patients were enrolled, including 21 men and 34 women, aged from 18 to 88 years. The PASI and body surface area were calculated for all patients. Blood samples were taken to evaluate serum concentration of YKL-40, as well as other inflammatory parameters, including CRP, ESR, white blood cell count, and neutrophil count. The measurements of YKL-40 level were performed by enzyme-linked immunosorbent assay (ELISA). Results YKL-40 serum concentration was significantly higher in psoriatic patients than in the control group. No correlations were found between YKL-40 levels and other clinical or laboratory parameters. Serum YKL-40 level was elevated in 81.8% patients, whereas CRP and WBC in 20% and 7.3% of patients, respectively. Conclusions YKL-40 could be considered as a useful biomarker of inflammation in psoriasis and is more sensitive than CRP or WBC. Increased YKL-40 may indicate psoriatic patients with a higher level of systemic inflammation, which may determine disease management.

Computational Analysis of Regulatory Network in Psoriasis by Top-Down Approach: An Initiation towards Identifying a Novel Biomarker to Diagnose and Treat Psoriasis in Future

In the era of post genomics, computational analysis of gene regulation in Psoriasis by the Top-down approach of computational biology to understand the pathology of disease and identifying a novel biomarker is a challenging task to execute. The challenge was approached on the context of Top-down approach [Annotation of Psoriasis associated genes from PubMed, DisGeNET and OMIM with text mining of regulators (microRNAs and Transcription Factors)] to construct and analyze the network by the approach of systems biology for understanding the disease pathology and predicting a novel and potential regulators to enhance the discovery of identifying a novel biomarker for Psoriasis in future.

Leucine-rich alpha-2 glycoprotein is an innovative biomarker for psoriasis linked to systemic inflammation

Leucine-rich alpha-2 glycoprotein is an innovative biomarker for psoriasis linked to systemic inflammation

251 IL17-producing treg as a potential biomarker for psoriasis

251 IL17-producing treg as a potential biomarker for psoriasis

A new biomarker for psoriasis.

A new biomarker for psoriasis.

Proteomic biomarkers for psoriasis and psoriasis arthritis

Although several new biomarkers have been recently proposed for psoriasis (Ps) and psoriasis arthritis (PsA), nothing is known about their diagnostic sensitivity and specificity, and their routine use. We therefore searched in-depth for new biomarker candidates using a biobank with EDTA-plasma from 158 individuals, patients and healthy controls. Samples from 6 selected pairs (patients against healthy controls) were searched proteomically using a workflow of extensive and precise design that is highly comprehensive. Subsequent verification was performed using ELISA and the entire biobank. By proteomic methods, 208 altered proteins were identified. Of these, 15 biomarker candidates were selected for verification. Of these 15, 4 individual parameters and 11 combinations significantly discriminated between patient and control groups. These individual parameters were Zn-α2-glycoprotein, complement C3, polymeric immunoglobulin receptor, and plasma kallikrein. Significant discrimination was obtained by combinations of 2 or 3 parameters. One combination seemed suitable for diagnosing PsA. Moreover, several candidates desmoplakin, complement C3, polymeric immunoglobulin receptor, and cytokeratin 17, correlated with PASI in all patients. This first comprehensive proteomic study on non-depleted plasma identified several biomarker candidates that have not been described before as well as some known from previous studies. Biological significanceOur non-gel proteomic analysis is based on the highly comprehensive and significantly optimized chromatographic protein pre-fractionation. The method allows a biomarker search in non-depleted plasma. The subsequent verification by ELISA identifies several biomarker-candidates for the unbiased diagnosis of psoriasis and psoriasis arthritis. Four of the identified candidate markers might be used individually. Combinations of several parameters improve the diagnostic sensitivity and specificity. The still not validated candidates form a reserve for further evaluation. Moreover, mass spectrometric data uncover several biomarker-candidates which show diverse protein species of the same protein with opposing changes in the same sample.

Serum biomarkers for diagnosis and assessment of severity in psoriasis

Introduction: Psoriasis is a common inflammatory and proliferative disease of the skin. The current gold standard for assessment of extensive psoriasis has been Psoriasis Area and Severity Index (PASI). However the limitations of using PASI score in clinical practice and research necessitates for search of biomarkers. Aims & Objectives: To determine the role of serum high sensitivity C-Reactive Protein (hs-CRP), Ceruloplasmin and Malondialdehyde (MDA) as biomarkers in psoriasis and their significance in assessment of disease severity in patients with mild, moderate and severe psoriasis. Materials & Methods: The study group consisted of 120 subjects of age group 20-50 years and of both sexes. Of these 40 patients had active psoriasis with PASI score 10 (Group 3) and 50 were healthy age and sex matched controls (Group 1). Results & Observations: The serum levels of CRP, ceruloplasmin and MDA are elevated in both the groups of psoriasis patients when compared to controls. The increase is statistically highly significant (p < 0.001). Very large positive correlation was obtained for hs-CRP and MDA values with PASI score in both the groups, while moderate correlation was obtained for Ceruloplasmin with PASI score. Conclusion: Finally, it can be concluded that hs-CRP, MDA and Ceruloplasmin levels can be used as biomarkers and also to assess the disease severity in psoriasis.

Among the S100 proteins, S100A12 is the most significant marker for psoriasis disease activity.

Psoriasis is a chronic skin disease with deregulation of proteins in the immune system. These proteins include members of the heterogeneous S100 family, which have been discussed as potential biomarkers for disease severity. The aim of this study was to evaluate the impact of S100A7, S100A8, S100A9 and S100A12 as possible markers for disease activity in patients with psoriasis skin disease. S100A7, S100A8, S100A9 and S100A12 mRNA expression was determined in the skin of patients with psoriasis and controls (N=341) by gene expression analyses. In addition, S100 serum levels were investigated by ELISA in an independent cohort of psoriasis patients (i) untreated, with different manifestations (skin/joints), (ii) under treatment (etanercept) and (iii) healthy controls, (N=55). All S100-subtypes included are significantly upregulated in psoriasis skin lesions when compared with atopic dermatitis, lichen ruber and healthy donors. In untreated psoriasis patients, S100A12-serum levels showed the closest association with disease activity (PASI) (r=0.542; P<0.01). Serum levels decreased under treatment with etanercept (P<0.05). Among the investigated S100-proteins, S100A12 showed the closest association with disease activity and therapeutic response and might therefore provide a valuable biomarker for psoriasis.

Patterns and functional roles of LINE-1 and Alu methylation in the keratinocyte from patients with psoriasis vulgaris.

Alterations in LINE-1 methylation are related to many diseases. The levels and patterns of LINE-1 hypomethylation were associated with a higher risk in developing several cancers, having a poorer prognosis and more aggressiveness. To evaluate the LINE-methylated status in psoriasis, LINE-1 methylation in various cells from patients with psoriasis, squamous cell carcinoma and normal controls were assessed by combined bisulfite restriction analysis of LINE-1. The results of the epigenetic changes for intragenic LINE-1 gene expression were also tested on two known expression microarrays. In patients with psoriasis, hypomethylation of LINE-1 and increase in %(u)C(u)C were prominent in the keratinocytes when compared with normal controls (P=0.014 and P=0.020, respectively). Alternatively, %(u)C(m)C was significantly lower in patients with severe psoriasis compared with mild psoriasis (P=0.022). The receiver-operating characteristic curve analysis indicated the high specificity and sensitivity of (u)C(u)C and (u)C(m)C in detecting psoriasis and severity of psoriasis. From expression array analysis, genes with LINE-1 were downregulated more than those genes without LINE-1 (P=3.84 × 10(-27) and P=2.14 × 10(-21), respectively). Modification in LINE-1 methylation may alter the gene expression resulting in a phenotypic change of the psoriatic skin. %(u)C(u)C and %(u)C(m)C may be used as biomarkers for psoriasis.