Multivariate analysis comparing patients currently aged under 40years with early onset psoriasis and patients with late onset psoriasis.

Multivariate analysis comparing patients currently aged under 40years with early onset psoriasis and patients with late onset psoriasis.</p

The Prevalence of Nonalcoholic Fatty Liver Disease and Related Metabolic Comorbidities Was Associated with Age at Onset of Moderate to Severe Plaque Psoriasis: A Cross-Sectional Study

<div><p>Nonalcoholic fatty liver disease (NAFLD) has been found to be highly prevalent in psoriatic patients. Adult onset psoriasis could be divided into either early or late onset psoriasis. The associations between NAFLD and related metabolic comorbidities and age at onset of psoriasis have not yet been investigated. Our study was to evaluate the associations between prevalence of NAFLD and related metabolic conditions and early, late, and childhood onset psoriasis. A cross-sectional observational study was conducted on patients with moderate to severe plaque psoriasis. Data on clinical characteristics of NAFLD and related metabolic diseases (diabetes, hypertriglyceridemia, hyperuricemia, and metabolic syndrome) were collected. The prevalence of NAFLD in 439 patients (mean: 51±14 years, range: 18–85 years) was 55.8%. NAFLD was frequently identified in early onset patients (74.2%), and this diagnosis was particularly common in patients currently younger than 40 (85.3%). Diabetes was the least prevalent component of metabolic syndrome in early onset patients with metabolic syndrome but the most often found component in late onset ones. Patients with childhood onset psoriasis had the lowest frequencies of all metabolic comorbidities except hyperuricemia among the three groups. In the multivariate analyses, early onset was independently and positively associated with NAFLD, hypertriglyceridemia and hyperuricemia and independently and negatively associated with diabetes among early and late onset patients. The results suggested prevalence of NAFLD and related metabolic comorbidities was associated with age at onset of moderate to severe plaque psoriasis. Early onset of psoriasis was independently associated with greater odds of NAFLD, hypertriglyceridemia, hyperuricemia and smaller odds of diabetes compared to late onset. Early onset patients have metabolic syndrome mainly related to lipid disorders and abnormal glucose metabolism was not often involved.</p></div

Prevalences of metabolic comorbidities in early onset patients currently aged 18–39 years, early onset patients currently aged over 40 years and late onset patients.

Prevalences of metabolic comorbidities in early onset patients currently aged 18–39 years, early onset patients currently aged over 40 years and late onset patients.</p

Multivariate analysis comparing patients with early onset psoriasis currently aged over 40 years and patients with late onset psoriasis.

<p>Multivariate analysis comparing patients with early onset psoriasis currently aged over 40 years and patients with late onset psoriasis.</p

Clinical characteristics and metabolic diseases according to age at onset (univariate analysis).

<p>Clinical characteristics and metabolic diseases according to age at onset (univariate analysis).</p

Multivariate analysis comparing patients with early onset psoriasis and childhood onset psoriasis.

<p>Multivariate analysis comparing patients with early onset psoriasis and childhood onset psoriasis.</p

Image_1_Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response.tif

Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines including IL-1β. How the immune response of monocytes is affected by metabolic internal environment in GPP remains unclear. Here, we performed a metabolomic and functional investigation of GPP serum and monocytes. We demonstrated a significant increase in IL-1β production from GPP monocytes. In GPP circulation, serum amyloid A (SAA), an acute-phase reactant, was dramatically increased, which induced the release of IL-1β from monocytes in a NLRP3-dependent manner. Using metabolomic analysis, we showed that GPP serum exhibited an amino acid starvation signature, with glycine, histidine, asparagine, methionine, threonine, lysine, valine, isoleucine, tryptophan, tyrosine, alanine, proline, taurine and cystathionine being markedly downregulated. In functional assay, under amino acid starvation condition, SAA-stimulated mature IL-1β secretion was suppressed. Mechanistically, at post-transcriptional level, amino acid starvation inhibited the SAA-mediated reactive oxygen species (ROS) formation and NLRP3 inflammasome activation. Moreover, the immune-modulatory effect of amino acid starvation was blocked by silencing general control nonderepressible 2 kinase (GCN2), suggesting the involvement of amino acid response (AAR) pathway. Collectively, our results suggested that decreased serum amino acids in GPP blunted the innate immune response in blood monocytes through AAR pathway, serving as a feedback mechanism preventing excessive inflammation in GPP.</p

Table_1_Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response.docx

Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines including IL-1β. How the immune response of monocytes is affected by metabolic internal environment in GPP remains unclear. Here, we performed a metabolomic and functional investigation of GPP serum and monocytes. We demonstrated a significant increase in IL-1β production from GPP monocytes. In GPP circulation, serum amyloid A (SAA), an acute-phase reactant, was dramatically increased, which induced the release of IL-1β from monocytes in a NLRP3-dependent manner. Using metabolomic analysis, we showed that GPP serum exhibited an amino acid starvation signature, with glycine, histidine, asparagine, methionine, threonine, lysine, valine, isoleucine, tryptophan, tyrosine, alanine, proline, taurine and cystathionine being markedly downregulated. In functional assay, under amino acid starvation condition, SAA-stimulated mature IL-1β secretion was suppressed. Mechanistically, at post-transcriptional level, amino acid starvation inhibited the SAA-mediated reactive oxygen species (ROS) formation and NLRP3 inflammasome activation. Moreover, the immune-modulatory effect of amino acid starvation was blocked by silencing general control nonderepressible 2 kinase (GCN2), suggesting the involvement of amino acid response (AAR) pathway. Collectively, our results suggested that decreased serum amino acids in GPP blunted the innate immune response in blood monocytes through AAR pathway, serving as a feedback mechanism preventing excessive inflammation in GPP.</p

Additional file 1 of Our Choice: study protocol for a randomized controlled trial for optimal implementation of psoriasis treatment by the integration of Chinese and western medicine

Additional file 1. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist: recommended items to address in a clinical trial protocol and related documents