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Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity.

ABSTRACT: Psoriasis vulgaris is a systemic disorder with an underlying immune dysregulation that predisposes to inflammatory skin lesions. Meanwhile, tumor necrosis factor alpha-induced protein 3 (TNFAIP3) has been described as a protective molecule against the deleterious effects of uncontrolled inflammation. In this study, we compared the expression levels of TNFAIP3 in blood and psoriatic skin biopsies from psoriatic patients versus those in normal individuals. Additionally, the levels of TNFAIP3 protein in psoriatic skin biopsies were compared to those in normal individuals. Thirty psoriatic patients and 30 healthy participants (control group) were enrolled. The expression levels of TNFAIP3 in blood and skin were measured by quantitative reverse transcription PCR, while the skin levels of TNFAIP3 protein were measured by western blot. Psoriatic patients showed significantly lower expression levels of TNFAIP3 in psoriatic skin and blood (P< 0.001) as well as of TNFAIP3 protein in psoriatic skin (P< 0.001) compared to controls. A significant lower expression of TNFAIP3 and TNFAIP3 protein in psoriatic skin was detected in moderate/severe cases compared to mild cases (P = 0.004 and 0.003 respectively). Moreover, a significant negative correlation was found between TNFAIP3 mRNA in psoriatic tissue and psoriasis area severity index values (rs = -0.382, P-value = 0.037). In conclusion, TNFAIP3 may serve as a predictive and prognostic biomarker in psoriatic patients. Enhancing the expression and/or function of TNFAIP3 in the affected cell type may be a promising therapeutic strategy.

SUBMITTER: Sahlol NY

PROVIDER: S-EPMC6532901 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity.

Sahlol Nahla Yassin NY Mostafa Marwa Salah MS Madkour Lamiaa Abd El-Fattah LAE Salama Dina Metwally DM

PloS one 20190523 5

Psoriasis vulgaris is a systemic disorder with an underlying immune dysregulation that predisposes to inflammatory skin lesions. Meanwhile, tumor necrosis factor alpha-induced protein 3 (TNFAIP3) has been described as a protective molecule against the deleterious effects of uncontrolled inflammation. In this study, we compared the expression levels of TNFAIP3 in blood and psoriatic skin biopsies from psoriatic patients versus those in normal individuals. Additionally, the levels of TNFAIP3 prote ...[more]

PMID: 31120955

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Project description:ObjectiveWe undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc).MethodsSkin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT-12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P-selectin glycoprotein ligand 1 (sPSGL-1) were examined in all patients enrolled in the GENISOS cohort (n = 266).ResultsEighty-two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC <70% predicted) in unsupervised hierarchical clustering analysis (P < 0.001). These genes included SELP, CCL2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. Among the FVC correlates, 8 genes (CCL2, HAPLN3, GPR4, ADCYAP1, WARS, CDC25B, PLP1, and STXBP6) also correlated with the MRSS. Immunofluorescence staining revealed that SELP and CCL2 were also overexpressed in affected skin and lung tissue from SSc patients compared to those from controls. Plasma levels of CCL2 and sPSGL-1 correlated with concomitantly obtained FVC values (r = -0.22, P = 0.001 and r = 0.17, P = 0.015, respectively). This relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti-topoisomerase I positivity, treatment with immunosuppressive agents, MRSS, disease type, and disease duration).ConclusionA limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ILD.

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Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity.

Publications

Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity.

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