Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis induced hepatobiliary injury in sickle cell disease.

Sickle cell disease (SCD) associated chronic hemolysis promotes oxidative stress, inflammation and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD related hepatobiliary injury has not been fully elucidated yet. Here, we show that chronic liver injury in SCD patients is associated with elevated levels of hepatic membrane bound CD163. Hemolysis and increase in hepatic heme, hemoglobin and iron levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that HO-1 positively regulates membrane bound CD163 expression independent of NRF2 signaling in SCD liver. We further demonstrate that of the interaction between CD163 and HO-1 is not dependent on CD163-hemoglobin binding. These findings indicate that CD163 is a potential biomarker of SCD associated hepatobiliary injury. Understanding the role of HO-1 in membrane bound CD163 regulation may help identify novel therapeutic targets for hemolysis induced chronic liver injury.

Liver-to-lung microembolic NETs promote gasdermin D-dependent inflammatory lung injury in sickle cell disease.

Acute lung injury, referred to as the acute chest syndrome, is a major cause of morbidity and mortality in patients with sickle cell disease (SCD), which often occurs in the setting of a vaso-occlusive painful crisis. P-selectin antibody therapy reduces hospitalization of patients with SCD by ∼50%, suggesting that an unknown P-selectin-independent mechanism promotes remaining vaso-occlusive events. In patients with SCD, intraerythrocytic polymerization of mutant hemoglobin promotes ischemia-reperfusion injury and hemolysis, which leads to the development of sterile inflammation. Using intravital microscopy in transgenic, humanized mice with SCD and in vitro studies with blood from patients with SCD, we reveal for the first time that the sterile inflammatory milieu in SCD promotes caspase-4/11-dependent activation of neutrophil-gasdermin D (GSDMD), which triggers P-selectin-independent shedding of neutrophil extracellular traps (NETs) in the liver. Remarkably, these NETs travel intravascularly from liver to lung, where they promote neutrophil-platelet aggregation and the development of acute lung injury. This study introduces a novel paradigm that liver-to-lung embolic translocation of NETs promotes pulmonary vascular vaso-occlusion and identifies a new GSDMD-mediated, P-selectin-independent mechanism of lung injury in SCD.

P-selectin deficiency promotes liver senescence in sickle cell disease mice.

Sickle cell disease (SCD) is caused by a homozygous mutation in the ß-globin gene, which leads to erythrocyte sickling, vasoocclusion, and intense hemolysis. P-selectin inhibition has been shown to prevent vasoocclusive events in patients with SCD; however, the chronic effect of P-selectin inhibition in SCD remains to be determined. Here, we used quantitative liver intravital microscopy in our recently generated P-selectin-deficient SCD mice to show that chronic P-selectin deficiency attenuates liver ischemia but fails to prevent hepatobiliary injury. Remarkably, we find that this failure in resolution of hepatobiliary injury in P-selectin-deficient SCD mice is associated with the increase in cellular senescence and reduced epithelial cell proliferation in the liver. These findings highlight the importance of investigating the long-term effects of chronic P-selectin inhibition therapy on liver pathophysiology in patients with SCD.

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease.

Sickle cell disease (SCD) is a monogenic disorder that affects 100,000 African Americans and millions of people worldwide. Intra-erythrocytic polymerization of sickle hemoglobin (HbS) promotes erythrocyte sickling, impaired rheology, ischemia and hemolysis, leading to the development of progressive liver injury in SCD. Liver resident macrophages and monocytes are known to enable the clearance of HbS, however, the role of liver sinusoidal endothelial cells (LSECs) in HbS clearance and liver injury in SCD remains unknown. Using real-time intravital (in vivo) imaging in the mice liver as well as flow cytometric analysis and confocal imaging of primary human LSECs, we show for the first time that liver injury in SCD is associated with accumulation of HbS and iron in the LSECs, leading to LSEC senescence. Hb uptake by LSECs was mediated by micropinocytosis. Hepatic monocytes were observed to attenuate LSECsenescence by accelerating HbS clearance in the liver of SCD mice, however, this protection was impaired in P-selectin-deficient SCD mice secondary to reduced monocyte recruitment in the liver. These findings are the first to suggest that LSECs contribute to HbS clearance and HbS induced LSEC-senescence promotes progressive liver injury in SCD mice. Our results provide a novel insight into the pathogenesis of hemolysis induced chronic liver injury in SCD caused by LSEC senescence. Identifying the regulators of LSEC mediated HbS clearance may lead to new therapies to prevent the progression of liver injury in SCD.

Dry eye syndrome symptoms in patients with psoriasis.

BACKGROUND: Psoriasis is one of the most common dermatoses associated with a variety of comorbidities. There have been some reports on its possible association with ocular disorders however dry eye syndrome (DES) in such patients has been poorly investigated. OBJECTIVES: To investigate the frequency of DES symptoms in psoriatic patients, also regarding psoriasis severity in PASI, manifestation and therapy. METHODS: 40 patients with psoriasis and 40 volunteers without dermatoses were enrolled in the study. They completed Ocular Surface Disease Index (OSDI) questionnaire and were objectively examined by IDRA® device to perform automatic interferometry, automatic meibography of lower eyelid glands, non-invasive break-up time (NIBUT), blink quality and tear meniscus height. RESULTS: Patients with psoriasis had statistically significantly thicker lipid layer (p = 0.0042 left eye, p = 0.0313 right eye) and greater loss of Meibomian glands compared to controls (p = 0.0128 left eye, p = 0.048 right eye). The patients had lower, although insignificantly, eye blink quality and tear meniscus height than the control group, as well as shorter NIBUT and higher score in OSDI. After the division of patients into two groups-with or without nails involvement/psoriatic arthritis/systemic treatment- we did not observe any significant differences between the groups. PASI did not correlate with any DES parameter. CONCLUSIONS: This is the first study of DES symptoms with an objective IDRA® analyzer. We managed to observe that patients with psoriasis have thicker lipid layer and higher Meibomian glands' loss in lower eyelids. Based on all assessed objective and subjective parameters psoriatics do not seem to have an increased risk of DES. The presence of psoriatic arthritis or nail involvement does not seem to be a predisposing factor for DES development. PASI probably cannot be a prognostic factor for any of the DES-associated parameters. Nevertheless, DES in psoriasis requires further research on bigger samples to establish reliable recommendations.

Intravital imaging reveals inflammation as a dominant pathophysiology of age-related hepatovascular changes.

Aging is the most significant risk factor for the majority of chronic diseases, including liver disease. The cellular, molecular, and pathophysiological mechanisms that promote age-induced hepatovascular changes are unknown due to our inability to visualize changes in liver pathophysiology in live mice over time. We performed quantitative liver intravital microscopy (qLIM) in live C57BL/6J mice to investigate the impact of aging on the hepatovascular system over a 24-mo period. qLIM revealed that age-related hepatic alterations include reduced liver sinusoidal blood flow, increased sinusoidal vessel diameter, and loss of small hepatic vessels. The ductular cell structure deteriorates with age, along with altered expression of hepatic junctional proteins. Furthermore, qLIM imaging revealed increased inflammation in the aged liver, which was linked to increased expression of proinflammatory macrophages, hepatic neutrophils, liver sinusoidal endothelial cells, senescent cells, and procoagulants. Finally, we detected elevated NF-κB pathway activity in aged livers. Overall, these findings emphasize the importance of inflammation in age-related hepatic vasculo-epithelial alterations and highlight the utility of qLIM in studying age-related effects in organ pathophysiology.

Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?

Diabetes Mellitus (DM) is amongst the most notable causes of years of life lost worldwide and its prevalence increases perpetually. The disease is characterized as multisystemic dysfunctions attributed to hyperglycemia resulting directly from insulin resistance (IR), inadequate insulin secretion, or enormous glucagon secretion. Insulin is a highly anabolic peptide hormone that regulates blood glucose levels by hastening cellular glucose uptake as well as controlling carbohydrate, protein, and lipid metabolism. In the course of Type 2 Diabetes Mellitus (T2DM), which accounts for nearly 90% of all cases of diabetes, the insulin response is inadequate, and this condition is defined as Insulin Resistance. IR sequela include, but are not limited to, hyperglycemia, cardiovascular system impairment, chronic inflammation, disbalance in oxidative stress status, and metabolic syndrome occurrence. Despite the substantial progress in understanding the molecular and metabolic pathways accounting for injurious effects of IR towards multiple body organs, IR still is recognized as a ferocious enigma. The number of widely available therapeutic approaches is growing, however, the demand for precise, safe, and effective therapy is also increasing. A literature search was carried out using the MEDLINE/PubMed, Google Scholar, SCOPUS and Clinical Trials Registry databases with a combination of keywords and MeSH terms, and papers published from February 2021 to March 2022 were selected as recently published papers. This review paper aims to provide critical, concise, but comprehensive insights into the advances in the treatment of IR that were achieved in the last months.

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.

Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD.

BACKGROUND: Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified. METHODS: To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed. Gene set enrichment analysis (GSEA) was used to identify the specific cell types contributing to the previously reported transcriptomic signatures. RESULTS: T-distributed stochastic neighbor embedding and clustering of scRNA seq data revealed a total of 17 distinct populations. Among them, the populations with more differentially expressed genes in cases vs. controls (log fold change >|0.4| and FDR = 0.05) were: monocytes (n = 1499); macrophages (n = 868) and ciliated epithelial cells (n = 590), respectively. Using GSEA, we found that only ciliated and cytotoxic T cells manifested a trend towards enrichment of the previously reported 127 regional emphysema gene signatures (normalized enrichment score [NES] = 1.28 and = 1.33, FDR = 0.085 and = 0.092 respectively). Among the significantly altered genes present in ciliated epithelial cells of the COPD lungs, QKI and IGFBP5 protein levels were also found to be altered in the COPD lungs. CONCLUSIONS: scRNA seq is useful for identifying transcriptional changes and possibly individual protein levels that may contribute to the development of emphysema in a cell-type specific manner.

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.

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.

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.

Indoxyl sulfate - the uremic toxin linking hemostatic system disturbances with the prevalence of cardiovascular disease in patients with chronic kidney disease.

BACKGROUND: During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play. The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition. METHODS: Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study. Coagulation factors, fibrinolytic parameters, adhesion molecules, endothelial dysfunction markers, oxidative stress as well as inflammation markers were examined using immune-enzymatic method. Indoxyl sulfate levels were assessed using high-performance liquid chromatography. Biochemical parameters were determined by routine laboratory techniques using an automated analyzers. All assessed parameters were compared with controls and subjected to cross-sectional statistical analysis. RESULTS: Elevated concentrations of indoxyl sulfate, the vast majority of parameters affecting hemostasis, and markers of renal insufficiency conditions were observed. Part of hemostatic factors, namely tissue factor, von Willebrand factor, thrombomodulin, soluble urokinase-type plasminogen activator receptor, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion protein were correlated with the fraction of indoxyl sulfate. A significant quantity of assessed parameters showed strong correlations with superoxide-dismutase, renal insufficiency rate, C-reactive protein, and neopterin. Levels of indoxyl sulfate were independently associated with markers of impaired endothelial function (thrombomodulin, adhesion molecules), oxidative stress (superoxide-dismutase) and monocytes activation determinant (neopterin), which indicate unconventional links between these systems and the role of indoxyl sulfate. Furthermore, parameters that correlated with the levels of indoxyl sulfate (von Willebrand factor, soluble urokinase-type plasminogen activator receptor, soluble intercellular adhesion molecule-1) were positively associated with the prevalence of cardiovascular disease in a CKD patients. CONCLUSIONS: The study demonstrated that in conditions of chronic exposure to uremic toxins, indoxyl sulfate seems to be one of the "missing links" between impaired renal function and prevalence of cardiovascular events, especially hemostatic disorders. The main functions of the action appear to be altered monocytes activation, intensified inflammatory process, and augmented oxidative stress by this uremic toxin.

Sexual dysfunctions in psoriatic patients.

Introduction: Psoriasis is one the most common skin diseases associated with a great decrease in the quality of patients' lives. Methods: We aimed to study sexual dysfunctions in psoriatic patients using the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men via an anonymous online survey. The study included 80 psoriatic patients and 75 controls without dermatoses. Results: There was a downward trend in the total IIEF score in psoriatic men compared to controls. 58% of male patients and 76% of controls had a normal IIEF score. There was no significant difference in IIEF between patients treated and not with systemic agents. 62% of female patients had a decreased FSFI score, whereas in the control group, the majority of subjects (54%) had a normal FSFI score. There was no significant difference in FSFI score between patients and controls. Female patients treated with systemic antipsoriatic agents had significantly worse lubrication, satisfaction with sexual life, and pain. Discussion: Our study has shown that the majority of questioned female psoriatic patients had sexual dysfunction according to FSFI, particularly they had worse satisfaction with sexual life and less sexual desire compared to women without psoriasis. The majority of male patients did not have sexual dysfunction according to IIEF, however, they had significantly worse overall satisfaction with sexual life and confidence to keep an erection. Systemic antipsoriatic treatment does not probably influence sexual dysfunctions in men but it does in women although we were not able to assess the severity or resolution of lesions after those treatments. However embarrassing, psoriatic patients should be questioned about their sexual lives by dermatologists, and more studies are needed to explore this matter.

Lung microvascular occlusion by platelet-rich neutrophil-platelet aggregates promotes cigarette smoke-induced severe flu.

Cigarette smoking is associated with a higher risk of ICU admissions among patients with flu. However, the etiological mechanism by which cigarette smoke (CS) exacerbates flu remains poorly understood. Here, we show that a mild dose of influenza A virus promotes a severe lung injury in mice preexposed to CS but not room air for 4 weeks. Real-time intravital (in vivo) lung imaging revealed that the development of acute severe respiratory dysfunction in CS- and flu-exposed mice was associated with the accumulation of platelet-rich neutrophil-platelet aggregates (NPAs) in the lung microcirculation within 2 days following flu infection. These platelet-rich NPAs formed in situ and grew larger over time to occlude the lung microvasculature, leading to the development of pulmonary ischemia followed by the infiltration of NPAs and vascular leakage into the alveolar air space. These findings suggest, for the first time to our knowledge, that an acute onset of platelet-driven thrombo-inflammatory response in the lung contributes to the development of CS-induced severe flu.

Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure.

Respiratory infection by Pseudomonas aeruginosa, common in hospitalized immunocompromised and immunocompetent ventilated patients, can be life-threatening because of antibiotic resistance. This raises the question of whether the host's immune system can be educated to combat this bacterium. Here we show that prior exposure to a single low dose of lipopolysaccharide (LPS) protects mice from a lethal infection by P. aeruginosa. LPS exposure trained the innate immune system by promoting expansion of neutrophil and interstitial macrophage populations distinguishable from other immune cells with enrichment of gene sets for phagocytosis- and cell-killing-associated genes. The cell-killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs and a prognostically favorable hypoinflammatory plasma biomarker subphenotype. Taken together, our study provides impetus for harnessing the potential of galectin-3-expressing neutrophils to protect from lethal infections and respiratory failure.

Osteopontin and Regulatory T Cells in Effector Phase of Allergic Contact Dermatitis.

Studies have shown that osteopontin (OPN) and regulatory T cells play a role in allergic contact dermatitis (ACD), but the mechanisms responsible for their function are poorly understood. The study aimed to determine CD4 T lymphocytes producing intracellular osteopontin (iOPN T cells) and assess the selected T lymphocyte subsets including regulatory T cells in the blood of patients with ACD. Twenty-six patients with a disseminated form of allergic contact dermatitis and 21 healthy controls were enrolled in the study. Blood samples were taken twice: in the acute phase of the disease and during remission. The samples were analyzed by the flow cytometry method. Patients with acute ACD showed significantly higher percentage of iOPN T cells compared with healthy controls which persisted during remission. An increase in the percentage of CD4CD25 and a reduced percentage of regulatory T lymphocytes (CD4CD25highCD127low) were also found in the patients with acute stage of ACD. The percentage of CD4CD25 T lymphocytes showed a positive correlation with the EASI index. The increase in the iOPN T cells can indicate their participation in acute ACD. The decreased percentage of regulatory T lymphocytes in the acute stage of ACD may be related to the transformation of Tregs into CD4CD25 T cells. It may also indicate their increased recruitment to the skin. The positive correlation between the percentage of CD4CD25 lymphocytes and the EASI index may be indirect evidence for the importance of activated lymphocytes-CD4CD25 in addition to CD8 lymphocytes as effector cells in ACD.

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.

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.