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.

The Potential Role of Serum Tau Protein (MAPT), Neuronal Cell Adhesion Molecule (NrCAM) and Neprilysin (NEP) in Neurodegenerative Disorders Development in Psoriasis-Preliminary Results.

Psoriasis is one of the most common dermatoses, which shortens patients' lives because of the wide comorbidity. However, little is known about its association with neurodegenerative diseases (NDs). We aimed to investigate whether psoriatics are at increased risk of NDs. Sixty patients with plaque-type psoriasis were enrolled into the study. Serum concentrations of tau protein (MAPT), neuronal cell adhesion molecule (NrCAM) and neprilysin (NEP), which are NDs biomarkers and have been hardly studied in psoriasis before, were measured before and after 12 weeks of treatment with acitretin or methotrexate. NrCAM and NEP concentrations were significantly lower in patients than controls, whereas MAPT higher (all p < 0.05). There was no association between these markers and psoriasis severity, BMI or disease duration. After the treatment the concentration of NrCAM and NEP significantly increased and MAPT decreased (p < 0.001, p < 0.05, p < 0.01, respectively). Methotrexate had significant influence on the concentrations of all markers, hence it seems to have neuroprotective properties. Psoriasis severity and duration do not seem to affect the risk of neurodegenerative process. Our results suggest that NDs could be considered as another comorbidity of psoriasis and that further research are needed in order to establish their definite association.

Fatty Acid-Binding Protein 7 (FABP-7), Glutamic Acid and Neurofilament Light Chain (NFL) as Potential Markers of Neurodegenerative Disorders in Psoriatic Patients-A Pilot Study.

Psoriasis and neurodegenerative diseases (NDs) are important medical, social and economic issues. The possible relationship of psoriasis and NDs has not been established yet. This study involved 60 patients with plaque-type psoriasis. Serum concentrations of fatty acid-binding protein 7 (FABP-7), glutamic acid (GA) and neurofilament light chain (NFL), which have been hardly studied in psoriasis before, were measured by ELISA before and after 12 weeks of treatment with acitretin or methotrexate. The concentration of FABP-7 and NFL in patients before the treatment was significantly higher than in the controls (p < 0.01, p < 0.001, respectively). After the treatment their concentration decreased, although FABP-7 did so insignificantly. The concentration of GA did not differ significantly between patients and controls and before and after the treatment but we found its negative correlation with CRP (p < 0.05). The duration of psoriasis does not seem to directly affect the risk of neurodegeneration and the severity only in patients with worse skin condition. Elevated FABP-7 and NFL, which are present in the brain, may be considered as potential indicators of NDs development in psoriatics, although it surely requires further research. GA might correspond with neuroinflammation in psoriasis. Systemic antipsoriatic therapy could be studied in order to improve cognitive impairment through lowering NDs biomarkers in some cases.

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.

Circulating MAdCAM-1 and ITGB7 in Patients with Plaque Psoriasis and Eruptive Lichen Planus-Preliminary Data.

Plaque psoriasis (PSO) and lichen planus (LP) are skin diseases with some similarities in pathogenesis, comorbidities, and clinical presentation. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and its ligand, α4ß7 integrin, are involved in inflammatory bowel diseases and liver dysfunctions, which occur more frequently in PSO and LP. Serum MAdCAM-1 and ITGB7 levels in patients with plaque PSO and eruptive LP have never been studied before. The study included 42 patients with PSO, 13 with LP, and 23 controls. Serum molecules levels were evaluated using the immune-enzymatic method. ITGB7 concentration was not statistically different, both in patients with PSO and LP, compared to controls (both p > 0.05). MAdCAM-1 level was significantly lower in PSO subjects than in controls (p = 0.041), whereas in the LP group, a downward trend was observed (p = 0.088) with p = 0.0455 in ANOVA. Multiple linear regression revealed independent associations between ITGB7 and HDL and BMI and RBC in the LP group. In psoriatic patients with elevated CRP, there was an upward trend for MAdCAM-1, and also a positive correlation between MAdCAM-1 and WBC. ITGB7 and MAdCAM-1 cannot serve as markers of disease activity or liver pathology neither in patients with PSO nor LP. MAdCAM-1 might play a role as an inflammation indicator in PSO and a beneficial influence on the lipid profile in LP.

Behçet's Disease in a Polish Patient: A Case Report.

Behçet's disease (BD) is a systemic autoinflammatory vasculitis. It occurs predominantly in Turkey but very rarely in Europe. The clinical manifestations of BD involve the skin and mucosal membranes; cardiovascular, gastrointestinal and nervous systems; and the eyes and joints. A 26-year-old man was repeatedly hospitalized at the Department of Dermatology of the Medical University of Bialystok. He had a family history of family members' deaths from unknown cause and a long personal history of recurring headaches and nonspecific pain in the chest as well as a 2-year history of recurring painful erosions on the oral mucosa. Recently, before admission to hospital, another erosion had appeared on the scrotum, which rapidly evolved into a painful ulceration. The patient also presented a large erosion in the area of the right hip and acne lesions. He consulted doctors of different specialties and underwent laboratory and imaging tests. Considering the symptoms, BD was diagnosed. Azathioprine was introduced, along with topical treatment. Great improvement of the skin lesions was achieved. He was later admitted to the department a few times for follow-up visits and remains in good general condition. BD is an extremely rare disease in Europe, especially in Poland. The fact that BD is a rare disease outside Asia leads to lower awareness and the possibility of not considering it in the differential diagnosis. The great diversity of symptoms also causes difficulties in tracking this disease. The various manifestations of BD require a broad spectrum of additional tests and an interdisciplinary approach to the patient.

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.

Proprotein Convertase Subtilisin/Kexin Type 9, Angiopoietin-Like Protein 8, Sortilin, and Cholesteryl Ester Transfer Protein-Friends of Foes for Psoriatic Patients at the Risk of Developing Cardiometabolic Syndrome?

Psoriasis is a systemic, immune-metabolic disease with strong genetic predispositions and autoimmune pathogenic traits. During psoriasis progression, a wide spectrum of comorbidities comes into play with the leading role of the cardio-metabolic syndrome (CMS) that occurs with the frequency of 30-50% amongst the psoriatic patients. Both conditions-psoriasis and CMS-have numerous common pathways, mainly related to proinflammatory pathways and cytokine profiles. Surprisingly, despite the years of research, the exact pathways linking the occurrence of CMS in the psoriasis population are still not fully understood. Recently published papers, both clinical and based on the basic science, shed new light into this relationship providing an insight into novel key-players proteins with plausible effects on above-mentioned interplay. Taking into account recent advances in this important medical matter, this review aims to discuss comprehensively the role of four proteins: proprotein convertase subtilisin/kexin type-9 (PSCK9), angiopoietin-like protein 8 (ANGPLT8), sortilin (SORT1), and cholesteryl ester transfer proteins (CEPT) as plausible links between psoriasis and CMS.

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.

Salivary Antioxidants and Oxidative Stress in Psoriatic Patients: Can Salivary Total Oxidant Status and Oxidative Status Index Be a Plaque Psoriasis Biomarker?

The aim of our research was to evaluate redox balance parameters and biomarkers of oxidative stress (OS) in nonstimulated and stimulated saliva as well as the blood of patients with plaque psoriasis compared to healthy controls. The study involved 40 patients with plaque psoriasis and 40 generally healthy subjects matched by age and gender to the study group patients. We assayed the concentration/activity of antioxidant enzymes: salivary peroxidase (Px), catalase (CAT), and superoxide dismutase (SOD) measured in unstimulated saliva (NWS), stimulated saliva (SWS), and erythrocytes. In plasma as well as NWS and SWS, we measured the concentration/activity of reduced glutathione (GSH), total antioxidant potential (TAC), total oxidative status (TOS), oxidative stress index (OSI), and markers of oxidative modification of proteins: advanced glycation end products (AGE), advanced oxidation protein products (AOPP), and lipid oxidation products: malondialdehyde (MDA) and total lipid hydroperoxide (LOOH). In NWS and SWS, we also evaluated the rate of reactive oxygen species (ROS) production. The concentration of Px, CAT, and SOD was significantly higher in NWS of patients with plaque psoriasis vs. healthy subjects. In SWS of psoriatic patients, we observed considerably higher concentration of Px and CAT, and in erythrocytes of patients with plaque psoriasis, the concentration of GPx and CAT was significantly higher compared to that in the controls. The levels of AOPP, AGE, MDA, and LOOH were considerably higher in NWS, SWS, and plasma of the study group compared to the controls. The concentration of total protein and salivary amylase was significantly lower in NWS and SWS of psoriatic patients compared to the healthy control. In the course of plaque psoriasis, we observed redox imbalances with prevalence of oxidation reactions. Mechanisms involved in the synthesis/secretion of proteins and activity of amylase were depressed in both glands of psoriatic patients; however, they were more inhibited in the parotid gland compared to the submandibular gland. TOS concentration and OSI value in NWS and SWS may serve as diagnostic biomarkers of plaque psoriasis.