Circulating ANGPTL8 as a Potential Protector of Metabolic Complications in Patients with Psoriasis.

Angiopoietin-like protein 8 (ANGPTL8) exerts pleiotropic effects, taking part in lipid and carbohydrate metabolism, inflammation, hematopoiesis and oncogenesis. So far, the exact molecular targets of ANGPTL8 remain poorly defined. We aimed to evaluate the serum concentration of ANGPTL8 in individuals with psoriasis and examine how systemic therapy affects the concentration of ANGPTL8. The study enrolled 35 patients with plaque-type psoriasis that were followed for 3 months of treatment with methotrexate or acitretin, and 18 healthy volunteers without psoriasis as controls. Serum ANGPTL8 concentrations were analyzed by ELISA and differences between groups were determined using Student's t-test or the Mann-Whitney test, while correlations were assessed using Spearman's rank test. The average concentration of ANGPTL8 differed significantly between the psoriasis group (before and after therapy) and the control group (p < 0.05). Significant negative correlations between ANGPTL8 and total cholesterol and LDL levels were noted (both p < 0.05). A significant increase in ANGPTL8 concentration was observed after acitretin (p < 0.05), whereas in patients treated with methotrexate the ANGPTL8 did not change significantly (p > 0.05). Additionally, a negative, statistically significant correlation with PASI was found after treatment (p < 0.05). Based on our study, it appears that elevated levels of ANGPTL8 may reduce the likelihood of atherogenic dyslipidemia in individuals with psoriasis, and treatment for psoriasis may impact the protective effects of ANGPTL8.

Potential Predictive Value of Serum Pentraxin 3 and Paraoxonase 1 for Cardiometabolic Disorders Development in Patients with Psoriasis-Preliminary Data.

Psoriasis is a systemic disease that is linked to cardiometabolic complications. Paraoxonase 1 (PON1) exerts anti-atherogenic properties. Pentraxin 3 (PTX3) is related to heart failure and atherosclerosis. We aimed to evaluate the protein levels in psoriatic patients and explore possible relations with disease activity, metaflammation parameters and systemic treatment. Thirty-three patients with plaque-type psoriasis and eleven healthy controls were enrolled in the study. Blood samples were collected before and after three months of therapy with acitretin or methotrexate. Serum proteins levels were evaluated using Bio-Plex 200 System. The mean serum pentraxin 3 level was significantly higher in patients with psoriasis, compared to controls (p < 0.01). Significant negative correlations between PTX3 with triglycerides in overweight patients, with glucose, cholesterol and triglycerides in obese patients, and with cholesterol and triglycerides in severe psoriatics were noted (all p < 0.05). After the treatment, PTX3 significantly decreased (p < 0.05). The mean serum PON1 in psoriatic patients did not differ, compared to the controls (p > 0.05). In psoriatics of normal weight, PON1 correlated negatively with liver enzymes activity (p < 0.05). PTX3 might exert a protective role in terms of cardiometabolic disorders development, especially in overweight and obese or most severe psoriatics. PON1 could serve as an indicator of the liver disorders in psoriasis.

Decreased levels of vaspin and its potential association with cardiometabolic risk in patients with psoriasis: preliminary results.

Introduction: Omentin and vaspin are considered to have beneficial effects preventing the development of metabolic disorders which are common comorbidities in psoriasis. Aim: To evaluate the serum level of these adipokines in psoriatic patients and elucidate possible associations with disease activity, metabolic or inflammatory parameters and systemic treatment. Material and methods: Thirty-three patients with active plaque-type psoriasis and 11 healthy controls participated in the study. Blood samples were collected before and after 3 months of treatment with acitretin or methotrexate. Results: Serum vaspin concentration in psoriatic patients was significantly lower than in the control group (p < 0.05). No correlation between adipokines and severity of disease evaluated with PASI was found. However, median vaspin levels decreased with the severity of skin lesions and the omentin level was higher in patients with severe disease versus those with moderate form (p < 0.05). The vaspin level correlated with BMI of psoriatic patients (p < 0.05), with cholesterol and triglycerides levels (p = 0.054, p = 0.049, respectively). No significant effect of systemic treatment on omentin levels was found. Regarding vaspin, we observed an upward trend in its concentration after treatment. Conclusions: Omentin and vaspin may play a modulating role in the systemic inflammation present in psoriasis and thus may contribute to the development of metabolic complications.

Serum Cholesteryl Ester Transfer Protein (CETP) and Sortilin (SORT) in Patients with Psoriasis with Relation to Systemic Treatment.

Psoriasis is a common inflammatory skin disease, which is tightly associated with metabolic disorders. Cholesteryl ester transfer protein (CETP) and sortilin (SORT) are molecules engaged in lipid metabolism of proatherogenic properties. They have been hardly ever studied in psoriasis before. Serum CETP and SORT concentrations were measured in 33 patients with plaque-type psoriasis before and after 12 weeks of treatment with methotrexate or acitretin. There was no significant difference in CEPT and SORT serum concentrations between patients and controls. Positive correlations between CETP after the treatment with acitretin and activity of transaminases (R = 0.65, R = 0.56, respectively) were noted. CETP was positively related with triglycerides (R = 0.49), glucose (R = 0.54) and CRP (R = 0.64) before the treatment with methotrexate, which all disappeared afterwards. Systemic therapy with methotrexate caused normalization of SORT concentration. There was significant correlation between SORT and WBC (p < 0.01) and CRP (p < 0.05). CETP and SORT cannot be used as individual biomarkers. Nevertheless, they show some interesting relations with other parameters. Increased concentration of CETP perhaps could investigated as a marker of liver side effects of acitretin treatment in psoriatics. SORT could be considered as a new indicator of metabolically induced inflammation in psoriasis. Methotrexate may be preferred in patients with high SORT concentrations. Further studies are needed to establish their exact role in psoriatic patients.

Galectin-3 as a Novel Multifaceted and Not Only Cardiovascular Biomarker in Patients with Psoriasis with Regard to Systemic Treatment-Preliminary Data.

Galectin-3 (gal-3) is a multifunctional regulator of various biological processes and diseases, which are common comorbidities in psoriasis. Data regarding potential diagnostic role of gal-3 in psoriasis are insufficient. Serum gal-3 levels were evaluated before and after twelve weeks of treatment with acitretin or methotrexate in 31 patients with plaque-type psoriasis and compared to 11 healthy control group. The mean serum galectin-3 level in patients with psoriasis was significantly higher compared to the control group (p < 0.01). In patients with obesity and long-lasting psoriasis (>20 years) positive relations of gal-3 and PASI were noted. In psoriatics with low gal-3 levels, positive correlations between the gal-3 and BMI, glucose level, and with the latter in short-lasting psoriasis (<20 years) were noted. In the long history of psoriasis, gal-3 was negatively correlated with lipids levels. The Gal-3 level might be a multifaceted modulator of the course of psoriasis and predictive factor of cardiometabolic comorbidities' development, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and short history of psoriasis are presumably at greater risk of diabetes. In patients with long-lasting psoriasis and concomitant obesity, gal-3 may exert a protective role against dyslipidemia or perhaps further CMD development.

High prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders in eastern Poland.

INTRODUCTION: The incidence of hepatitis E virus (HEV) infections in Poland is largely unknown. This study aimed to describe seroprevalence of markers of HEV infection among patients with immunodeficiency of diverse etiology and patients with advanced chronic liver diseases. MATERIAL AND METHODS: Four hundred fifty patients were enrolled; among them, 180 persons were solid organ transplant recipients, 90 patients were HIV-infected and 180 persons had confirmed liver cirrhosis of different etiology. Serum anti-HEV-IgG, IgM antibodies and HEV-antigen were detected by ELISA (Wantai, China). RESULTS: In the group of transplant recipients, serum anti-HEV-IgG antibodies were detected in 40.6%, IgM in 1.1% and HEV-Ag in 2.8% of subjects. In the HIV-infected population 37.7% had anti-HEV-IgG, 1.1% had anti-HEV-IgM and none had HEV-Ag. Among patients with advanced chronic liver diseases the highest prevalence of anti-HEV-IgG was recorded in alcohol-related liver cirrhosis (52.1%) (p = 0.049). In the population of all liver cirrhotics anti-HEV-IgG seroprevalence was 48.3%, anti-HEV-IgM seroprevalence was 5.0% and HEV-Ag seroprevalence was 1.7%. Older age and male gender were significant risk factors associated with increased anti-HEV-IgG prevalence, p = 0.0004 and p = 0.02, respectively. CONCLUSIONS: In this large cohort a high seroprevalence of anti-HEV-IgG was detected in comparison to other European countries, with the highest rates in patients with alcoholic liver disease and in transplant recipients.

Elevated circulating Krüppel-like factor 4 level as a novel independent marker of the proatherogenic risk in patients with psoriasis: a preliminary study.

INTRODUCTION: Krüppel-like factor 4 (KLF4) is a transcription factor of anti-inflammatory and anti-thrombotic properties not studied in psoriasis yet. AIM: To analyze the clinical value of the serum KLF4 level in psoriatics and elucidate the interplay between disease activity, metabolic or inflammatory parameters and systemic therapy. MATERIAL AND METHODS: The study enrolled thirty-four psoriatics and fifteen healthy subjects. Blood samples were collected before and after twelve weeks of treatment with methotrexate or acitretin. Serum KLF4 levels were measured using immune-enzymatic method. RESULTS: Serum KLF4 levels in psoriatic patients did not statistically differ comparing to the controls (p > 0.05). However, in severe psoriasis, KLF4 was significantly higher than in healthy ones before treatment and normalized after treatment to baseline levels of controls (p < 0.05, p > 0.05, respectively). KLF4 positively correlated with body mass index (p = 0.038) but not with psoriasis severity, nor inflammatory or metabolic markers. Interestingly, many pro-atherogenic parameters were shown as variables independently predicting the levels of KLF4. No significant effect of three-month systemic treatment on KLF4 was found. CONCLUSIONS: KLF4 may be a novel independent indicator of the proatherogenic risk in psoriatics, especially with a severe form or obesity.

Higher Serum Selenoprotein P Level as a Novel Inductor of Metabolic Complications in Psoriasis.

Selenoprotein P (SeP), a member of hepatokines, is involved in the development of various metabolic diseases closely related to psoriasis, but it has not been explored in that dermatosis so far. The study aimed to evaluate the clinical value of serum SeP concentrations in patients with psoriasis and its interplay between disease activity, metabolic or inflammatory parameters and systemic therapy. The study included thirty-three patients with flared plaque-type psoriasis and fifteen healthy volunteers. Blood samples were collected before and after three months of treatment with methotrexate or acitretin. Serum SeP levels were evaluated using the immune-enzymatic method. SeP concentration was significantly higher in patients with psoriasis than in the controls (p < 0.05). Further, in patients with severe psoriasis, SeP was significantly increased, compared with the healthy volunteers before treatment, and significantly decreased after (p < 0.05, p = 0.041, respectively). SeP positively correlated with C-reactive protein and platelets and negatively with red blood counts (p = 0.008, p = 0.013, p = 0.022, respectively). Therapy resulted in a significant decrease in SeP level. Selenoprotein P may be a novel indicator of inflammation and the metabolic complications development in psoriatics, especially with severe form or with concomitant obesity. Classic systemic therapy has a beneficial effect on reducing the risk of comorbidities by inhibiting SeP.

Methotrexate Decreases the Level of PCSK9-A Novel Indicator of the Risk of Proatherogenic Lipid Profile in Psoriasis. The Preliminary Data.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) exerts an important role in inflammatory processes, lipids homeostasis, and cardiometabolic disorders that are closely associated with psoriasis. The aim of the study was to analyze the clinical and diagnostic value of serum PCSK9 concentrations and their connections with disease severity, inflammation, metabolic syndrome, and impact of systemic therapies in psoriatic patients. The study enrolled thirty-five patients with active plaque-type psoriasis and eighteen healthy volunteers served as controls. Blood samples were obtained before and after 12 weeks of treatment with methotrexate or acitretin. Serum PCSK9 concentrations were measured by the ELISA (Enzyme-Linked Immunosorbent Assay) commercial kits. Morphological and biochemical parameters were assayed using routine laboratory techniques. Psoriatic patients showed significantly elevated levels of PCSK9 compared to controls (p < 0.01), mostly in patients with a mild and moderate course of psoriasis. PCSK9 concentrations correlated positively with BMI and triglyceride levels (p < 0.05). Interestingly, PCSK9 had a strong negative correlation with low-density lipoprotein levels and total cholesterol (p < 0.05). Three months of monotherapy with methotrexate significantly reduced PCSK9 level (p < 0.05), on the contrary, the acitretin group showed a further increase of PCSK9 levels (p < 0.05). PCSK9 seems to be a novel marker of psoriasis and a putative explanation of lipid disturbances, which are common in patients with psoriasis and are vital for the further developing of metabolic syndrome. Methotrexate should be considered as a treatment of choice in patients with an elevated PCSK9 concentration.

Lp-PLA2 as a promising predictor of comorbidities in patients with severe psoriasis.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a well- known risk factor of atherosclerotic vascular diseases which are common comorbidities in psoriasis. The aim of this study was to evaluate serum Lp-PLA2 level in psoriatic patients and elucidate possible associations with disease activity, metabolic or inflammatory parameters and systemic treatment.Methods: We enrolled 33 patients with active plaque-type psoriasis and 11 healthy controls. Blood samples were collected before and after 3 months of systemic treatment with acitretin or methotrexate. Serum Lp-PLA2 level were evaluated by enzyme-linked immunosorbent assay.Results: Serum Lp-PLA2 level in patients with psoriasis did not statistically differ comparing to the control group (p = .2). However, in patients with severe psoriasis Lp-PLA2 was significantly higher than in the controls before and after treatment (p = .03, p = .01, respectively). The lipase did not correlate with BMI (p = .22); however, a statistical significance was noted between psoriatics with obesity compared to the controls (p = .03). No significant effect of systemic treatment combined (p = .5) nor separately with acitretin (p = .5) or methotrexate (p = .1) on the Lp-PLA2 level was found, despite clinical improvement.Conclusion: Lp-PLA2 assay might be helpful in assessment of the risk of cardiometabolic comorbidities development especially in patients with severe psoriasis and obesity.

The Level of FGF 21 as a New Risk Factor for the Occurrence of Cardiometabolic Disorders amongst the Psoriatic Patients.

Fibroblast growth factors 21 and 23 are used as markers of cardiometabolic disorders which are common comorbidities in psoriasis. The study aimed to evaluate the serum level of these factors in psoriatic patients and elucidate the possible interplay between disease activity, metabolic or inflammatory parameters, and systemic treatment. A total of 33 patients with active plaque-type psoriasis and 11 healthy controls were enrolled in the study. Patients were divided into subgroups based on their BMI, disease severity, and treatment. Blood samples were collected at the beginning of the study and after 3 months of systemic treatment with acitretin or methotrexate. Serum FGF21 levels in psoriatic patients were higher versus control group (p < 0.05). FGF21 levels regarding psoriasis activity were significantly increased in all three subgroups compared to the controls (p < 0.05). Regarding FGF23, no significant changes were found beside positive correlation with aspartate transferase (p < 0.05). No significant effect of systemic treatment on FGF21 and FGF23 levels was found. Interestingly, a nearly threefold decrease in FGF21 concentration after acitretin-based treatment was observed (p < 0.05). After methotrexate therapy, FGF21 levels remained unchanged. FGF21 levels might be helpful in prediction of the risk of cardiometabolic comorbidities development especially in patients with severe psoriasis and obesity.

Adipocyte Fatty Acid-Binding Protein as a Novel Marker of Psoriasis and Clinical Response to Acitretin.

Psoriasis is a systemic disease associated with metabolic syndrome and cardiometabolic diseases. Adipocyte fatty acid-binding protein (A-FABP, FABP4) is a relevant mediator of lipid metabolism and several comorbidities development. Aim of the study was to explore the possible role of FABP4 in psoriasis and assess its relationship with disease activity, inflammation or metabolic disturbances, and impact of systemic treatment. Fasting blood samples were obtained from 33 patients with active plaque-type psoriasis before and after 12 weeks of therapy and from 11 healthy volunteers. Serum FABP4 concentrations were analyzed by the enzyme-linked immunosorbent assay (ELISA) and statistically analyzed for their correlations with clinical outcomes and the treatment introduced. Serum FABP4 levels were significantly increased in psoriatics compared to controls (p = 0.03). No relationship between the protein and psoriasis severity expressed through psoriasis area and severity index (PASI) was noted (p = 0.57). FABP4 did not correlate with CRP (p = 0.41), lipid profile, and body mass index (BMI) nor the glucose level or liver enzyme activity. FABP4 significantly correlated with morphotic blood elements. After total therapy, FABP4 did not statistically change (p = 0.07), but significantly decreased after administering acitretin (p = 0.03). FABP4 is a potential marker of psoriasis and clinical outcome after therapy with acitretin. Adipocyte-type FABP may be related to hematological disorders or obesity-mediated comorbidities in psoriasis.

Liver fatty acid-binding protein might be a predictive marker of clinical response to systemic treatment in psoriasis.

Fatty acid-binding proteins play an inconclusive role in lipid metabolism and cardiometabolic diseases (CMDs) which are closely related with psoriasis. Aim of the study was to investigate the diagnostic value of serum liver fatty acid-binding protein (FABP1) level and associations with disease severity, inflammation or metabolic parameters and influence of systemic treatment in psoriatic patients. The study included thirty-three patients with active plaque-type psoriasis and eleven healthy volunteers. Blood samples were obtained before and after 12 weeks of therapy with methotrexate and acitretin. Serum FABP1 concentrations were analyzed by the enzyme-linked immunosorbent assay. Statistical analysis was performed for correlation of FABP1 with anthropometric, metabolic or inflammatory indices and treatment used. Serum liver-type FABP levels were significantly increased in psoriatic patients compared to the controls (p < 0.001). No statistical correlations between FABP1 and PASI (p = 0.25) was noted, however patients with severe psoriasis had the highest level of FABP1. No significance with metabolic parameters was obtained, beside a positive significant relation with BMI after therapy (p = 0.03). Liver-type FABP significantly correlated with CRP (p = 0.01) and morphotic blood elements. Systemic treatment combined resulted in significant decrease of FABP1 (p = 0.04), regardless of the drug: p = 0.1 in acitretin group, p = 0.3 in methotrexate group. Liver-type FABP might be a novel marker of psoriasis and predictor of clinical response to systemic therapy. FABP1 could be involved in CMDs risk assessment and perhaps link psoriasis with hematological disorders.

Chronic hepatitis B virus infection is associated with decreased serum 25(OH)D concentration in non-cirrhotic patients.

AIM OF THE STUDY: Recent reports provide evidence for the immunomodulatory properties of vitamin D. Decreased vitamin D levels may contribute to the progression of liver disease in hepatitis B virus (HBV) infection. This study aims to assess serum 25(OH)D in patients with chronic HBeAg-negative HBV (CHB) infection at different phases of disease. MATERIAL AND METHODS: Fifty-eighty patients with CHB, 10 with a history of HBsAg/anti-HBs seroconversion, were enrolled. The control group consisted of 9 healthy volunteers. Serum 25(OH)D concentration was assessed by ELISA. RESULTS: Serum 25(OH)D concentration was significantly lower in the CHB group in comparison to the HC group. It did not differ across the consecutive phases of the HBeAg-negative HBV infection. Negative correlations between serum 25(OH)D and alanine aminotransferase (ALT) as well as frequency of peripheral blood monocytes were observed. Serum 25(OH)D in samples collected in winter was significantly lower in comparison to the pool of samples collected in the summer. Serum 25(OH)D concentration was not associated with the phases of HBV-infection, HBV viral load, APRI or liver histology. CONCLUSIONS: Serum 25(OH)D is significantly decreased in HBV infection irrespectively of the phase of the infection and negatively correlates with serum ALT level, which may reflect the deterioration of liver function. Based on our results, we can conclude that the role of vitamin D in the immune control of HBV infection is probably irrelevant.