MicroRNA profiling of psoriatic skin identifies 11 miRNAs associated with disease severity

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m−2h−1 and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m−2 h−1) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment.

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Temporal Correlations of Skin and Blood Metabolites with Clinical Outcomes of Biologic Therapy in Psoriasis

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa009 ◽

2020 ◽

Vol 5 (5) ◽

pp. 877-888 ◽

Cited By ~ 1

Author(s):

Ewelina P Dutkiewicz ◽

Kai-Ta Hsieh ◽

Pawel L Urban ◽

Hsien-Yi Chiu

Keyword(s):

Disease Severity ◽

Biologic Therapy ◽

Sampling Technique ◽

Mass Spectrometric ◽

Psoriatic Skin ◽

Dynamic Changes ◽

Biologic Drugs ◽

Temporal Correlations ◽

Blood Specimens ◽

Metabolic Biomarkers

Abstract Background Psoriasis is an inflammatory skin disease causing multisystem effects. Introduction of biologic drugs has led to promising results in treatment of this disease. Here, we carry out time-dependent profiling of psoriasis-related putative metabolic biomarkers. Methods Skin excretion specimens were collected from 17 patients with psoriasis treated with biologics for 7 months. Blood specimens were obtained from the same patients at intervals of 1–3 months. A hydrogel micropatch sampling technique was implemented to collect lesional (L) and nonlesional (NL) skin specimens. The collected skin and blood specimens were analyzed by mass spectrometric methods. Results The metabolites present on L skin—in particular, choline, and citrulline—showed greater dynamics, corresponding to the resolution of psoriasis than the metabolites present in NL skin or blood. Choline levels in L skin and blood correlated positively, while citrulline correlated negatively with the severity of individual psoriasis plaques and general disease severity, respectively. Nevertheless, the correlations between the metabolite levels in blood and general disease severity were weaker than those between the metabolite levels on L skin and severity of individual plaques. The changes of these skin metabolites were more prominent in the responders to the treatment than in the nonresponders. Conclusions The results support the feasibility of characterizing dynamic changes in psoriatic skin metabolic proﬁles with the hydrogel micropatch probes and mass spectrometric tests. The study represents one of few attempts to explore relationships between skin and blood metabolite concentrations. However, practical use of the methodology in close clinical monitoring is yet to be demonstrated.

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Serum Levels of TNF-α, IL-12/23p40, and IL-17 in Plaque Psoriasis and Their Correlation with Disease Severity

Journal of Immunology Research ◽

10.1155/2014/467541 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Aikaterini Kyriakou ◽

Aikaterini Patsatsi ◽

Timoleon-Achilleas Vyzantiadis ◽

Dimitrios Sotiriadis

Keyword(s):

Disease Severity ◽

Plaque Psoriasis ◽

Solid Phase ◽

Severity Index ◽

Serum Levels ◽

Rank Test ◽

Psoriatic Skin ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Psoriasis Area Severity Index

A case-control study was performed to assess the serum levels of TNF-α, IL-12/23p40, and IL-17 in patients with plaque psoriasis, compare them with healthy controls, and correlate them with disease severity, as represented by Psoriasis Area Severity Index (PASI). 32 consecutively selected, untreated patients with active, chronic plaque psoriasis were recruited and compared to 32 age- and sex-matched healthy controls. Serum cytokine levels were determined by solid phase sandwich enzyme linked immunosorbent assay (R&D Systems Europe, Ltd.). The mean serum levels of TNF-αwere significantly higher in psoriatic patients compared to those of controls (Mann-WhitneyUtest;P=0.000). However, the median serum levels of neither IL-12/23p40 nor IL-17 differ significantly between the 2 groups (Mann-WhitneyUtest;P=0.968andP=0.311, resp.). No significant correlations were found between PASI and any of the cytokine serum levels (Spearman’s rank test;P>0.05). Despite the well-evidenced therapeutic efficacy of biologic agents targeting TNF-α, IL-12/23p40, and IL-17, serum levels of TNF-α, IL-12/23p40, and IL-17 do not seem to correlate with the severity of psoriatic skin disease in untreated patients, as represented by PASI. Further investigation may add more data on the pathogenetic cascade of psoriasis.

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Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

BioMed Research International ◽

10.1155/2021/6656622 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Xiaoting Gong ◽

Wei Wang

Keyword(s):

Mast Cells ◽

Nk Cells ◽

Disease Severity ◽

Immune Cell ◽

Γδ T Cells ◽

Innate Immune ◽

Innate Immune Cell ◽

Psoriatic Skin ◽

Psoriatic Plaque ◽

Core Genes

Psoriasis is an inflammatory skin disease with substantial morbidity. Numerous patients with psoriasis experience recurrence after therapy. The underlying mechanism about psoriasis is still not fully understood. Some evidences suggest that innate immunity may play an unexpected and important role in active severe psoriasis. In this work, the deconvolution algorithm CIBERSORT was conducted to identify the infiltration of innate immune cells and related core genes in psoriatic plaque. Datasets from the Gene Expression Omnibus, including skin samples from 405 psoriasis patients and 91 healthy donors, were downloaded for analysis. Considerable differences of the innate immune cell composition were uncovered between psoriatic plaque and control skin. Results revealed that γδ T cells, resting NK cells, M0 macrophages, M1 macrophages, activated dendritic cells, and neutrophils were significantly increased in psoriatic skin, while resting mast cells and active NK cells were significantly decreased. Moreover, the proportion of M0 macrophages or resting mast cells was found to be associated with disease severity. Spearman correlation analysis suggests that RORC and S100A12 genes were related to disease severity, while genes including S100A12, CLEC4C, IL-19, AIM2, IL-17F, and PPARGC1A were correlated with biologic treatment response. In conclusion, this work displays innate immune status in psoriatic skin and provides novel clues for clinical decisions and mechanism study.

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RNA sequencing of a large number of psoriatic patients identifies 131 novel miRNAs and 11 miRNAs associated with disease severity

10.1101/2021.01.27.21250590 ◽

2021 ◽

Author(s):

Å.Ø. Solvin ◽

K. Chawla ◽

L.C. Olsen ◽

K. Danielsen ◽

M. Jenssen ◽

...

Keyword(s):

Disease Severity ◽

Functional Enrichment ◽

Psoriatic Skin ◽

Comprehensive Overview ◽

Specific Expression ◽

Functional Studies ◽

Differentially Expressed Mirnas ◽

Skin Biopsies ◽

Meta Analyses ◽

And Control

AbstractBackgroundMicroRNAs are small regulatory molecules that are dysregulated in psoriasis. Despite previous efforts, much is unknown about the regulatory mechanisms of psoriasis genetics and their contributions to disease development and activity.ObjectivesTo globally characterize the miRNAome of psoriatic skin in a large sample of psoriatic cases and controls for increased understanding of psoriasis pathophysiology.MethodsSkin biopsies from psoriatic cases (n=75) and non-psoriatic controls (n=57) were RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n=24, controls, n=20), increasing the number of psoriatic cases four-fold from previously published studies. Differential expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell specific analyses were performed.ResultsWe identified 439 significantly differentially expressed miRNAs (DEMs), of which 131 were novel and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in all psoriatic skin. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including ‘thyroid hormone signaling’, ‘insulin resistance’ and various infectious diseases. Cell specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells.ConclusionsWe have provided the most comprehensive overview of the miRNome in psoriatic skin to date and identified a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.

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Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

10.21203/rs.3.rs-63594/v1 ◽

2020 ◽

Author(s):

Xiaoting Gong ◽

Wei Wang

Keyword(s):

Mast Cells ◽

Nk Cells ◽

Disease Severity ◽

Immune Cell ◽

Γδ T Cells ◽

Innate Immune ◽

Innate Immune Cell ◽

Psoriatic Skin ◽

Psoriatic Plaque ◽

Core Genes

Abstract Background: Psoriasis is an inflammatory skin disease with substantial morbidity. Numerous patients with psoriasis experience recurrence after therapy. The underlying mechanism about psoriasis is still not fully understood. Some evidences suggest that innate immunity may play an unexpected and important role in active severe psoriasis. In this work, the deconvolution algorithm CIBERSORT was conducted to identify the infiltration of innate immune cells and related core genes in psoriatic plaque.Results: Datasets from the Gene Expression Omnibus, including 407 psoriasis lesional, 373 non-lesional and 91 normal skin samples, were downloaded for analysis. Considerable differences of the innate immune cell composition were uncovered between psoriatic plaque and control skin. Results revealed that γδ T cells, resting NK cells, M0 macrophages, M1 macrophages, activated dendritic cells and neutrophils were significantly increased in psoriatic skin, while resting mast cells and active NK cells were significantly decreased. Moreover, the proportion of M0 macrophages or resting mast cells was found to be associated with disease severity. Spearman correlation analysis suggests that RORC and S100A12 genes were related to disease severity, while genes including S100A12, CLEC4C, IL-19, AIM2, IL-17F, PPARGC1A, were correlated with biologics treatment response.Conclusions: Collectively, this work displays innate immune status in psoriatic skin, and provides novel clues for clinical decisions and mechanism study.

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Platelet-neutrophil aggregates promote skin pathology in psoriasis

10.1101/526236 ◽

2019 ◽

Author(s):

Franziska Herster ◽

Zsofia Bittner ◽

Marius Cosmin Cordrea ◽

Nate Archer ◽

Martin Heister ◽

...

Keyword(s):

Disease Severity ◽

Psoriasis Patient ◽

Surface Antigens ◽

Skin Lesions ◽

Human Neutrophils ◽

Psoriatic Skin ◽

List Type ◽

Platelet Surface ◽

Cardiovascular Comorbidities

AbstractPsoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in vivo ameliorated disease severity significantly, indicating that the intimate relationship of PMNs and platelets may be relevant for psoriasis pathology and disease severity, and potentially for psoriasis-associated cardiovascular comorbidities.Key pointsHuman neutrophils in psoriasis patient blood show a distinct ‘platelet signature’ of surface antigensPlatelets congregate with neutrophils in psoriatic skin lesionsCirculating platelets contribute to psoriasis skin pathology

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