Iwona Flisiak

Plasma TGF-β1, TIMP-1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity

Abstract Plasma levels of transforming growth factor (TGF)-β1, tissue inhibitors of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-1 and interleukin (IL)-18 when analyzed separately demonstrate an association with psoriasis severity and treatment efficacy. To determine the highest correlation with the Psoriasis Area and Severity Index (PASI) score we carried out an analysis of these four proteins combined as the TTMI score. Concentrations of proteins were measured using an enzyme immunoassay in the plasma of 32 patients with chronic plaque-type psoriasis. The concentration of each biomarker was multiplied by the respective coefficient and the final individual TTMI score was the sum of these four values. TGF-β1, TIMP-1 and IL-18 demonstrated significant positive correlation, whereas MMP-1 demonstrated significant negative correlation with the PASI score. The TTMI score calculated for individual patients varied from −79 620 to 145 713 (43 050±8081) and demonstrated significant correlation with the PASI score. The lowest TTMI mean value was observed in patients with a PASI score <16 and the highest value was in patients with a PASI score >20. The combined measurement of plasma TGF-β1, TIMP-1, MMP-1 and IL-18 has superior value as a biomarker of psoriasis activity in comparison with their separate analysis.

Update on alisporivir in treatment of viral hepatitis C

Introduction: There are two classes of anti-hepatitis C virus (HCV) agents currently in development: direct-acting antivirals (DAA) and host-targeting antivirals (HTA). Cyclophilin inhibitor alisporivir (ALV), previously known as Debio-025 is the most advanced HTA in development. Areas covered: Experimental and clinical studies demonstrated that ALV has high genetic barrier and no cross-resistance to DAA. Pharmacokinetic studies showed a profile suitable for once-daily administration. Phase I and II studies confirmed strong HCV suppression and that addition of ALV to pegylated IFNα (PegIFNα) and ribavirin (RBV) can improve their efficacy significantly. ALV was well tolerated and prevalence of the most frequent clinical and laboratory adverse events was similar to PegIFNα/RBV. Hyperbilirubinemia was the only significant adverse event related to ALV, but it was transient, reversible and not associated with hepatotoxicity or cholestasis. Expert opinion: ALV is pangenotypic, with once-daily administration and safe, therefore medication can be easy and flexible. There is still a need of data in difficult-to-treat populations and genetic studies allowing selection of possible non-responders. Registration of ALV for IFN-based treatment is expected within 3 years, but ALV is also a good candidate for IFN-sparing combinations with DAA.

Plasma transforming growth factor β1 as a biomarker of psoriasis activity and treatment efficacy

Transforming growth factor-β1 (TGFβ1) is thought to be an inhibitor of the keratinocyte hyperproliferation associated with psoriasis. The aim of this study was to evaluate plasma TGFβ1 and TGFβ2 concentrations in psoriatic patients as possible indicators of treatment efficacy. TGFβ concentrations were measured in the plasma of 26 patients with psoriasis using an enzyme immunoassay and analysed with respect to the psoriasis area and severity index (PASI) before and after treatment with salicylic acid and/or sulphur followed by dithranol ointment. Baseline plasma concentrations of both TGFβ1 and TGFβ2 (20.3±2.2 ng ml−1 and 0.14±0.02 ng ml−1, respectively) did not differ significantly from control values (18.3±1.6 ng ml−1 and 0.14±0.03 ng ml−1, respectively). However, a significant positive correlation (r=0.69) between the baseline PASI and TGFβ1, but not TGFβ2, values was demonstrated. The pretreatment TGFβ1 concentration in patients with a PASI ≥15 (26.6±3.2 ng ml−1) was significantly higher than control values. There were no significant elevation of pretreatment TGFβ1 concentrations in patients with a PASI<15, or with respect to TGFβ2 in both groups. Treatment caused a significant decrease in TGFβ1, but only in patients with a PASI≥15. Patients with baseline TGFβ1 concentrations exceeding the mean of the control group had a PASI value that was significantly higher than that of patients with a TGFβ1 concentration below the mean of the controls. These results confirmed an association between plasma TGFβ1 concentration and psoriasis severity, and demonstrated its normalization during treatment. Measurement of TGFβ1 in plasma should be considered as a possible biomarker of psoriasis activity during its management.

Plasma and scales levels of interleukin 18 in comparison with other possible clinical and laboratory biomarkers of psoriasis activity

Abstract The aim of the study was to assess plasma and scales levels of interleukin (IL) 18 collected from psoriatic patients with different disease activity. IL-18 concentrations were measured using an enzyme immunoassay in the plasma and scales of 34 patients with chronic plaque type psoriasis. IL-18 levels were analysed with respect to plasma-transforming growth factor β1 (TGF-β1), the disease duration and the duration of the present relapse, and psoriasis area and severity index (PASI). Plasma IL-18 concentration varied from 90 to 1300 pg ml−1 and means (368.2±42.4 pg ml−1) were significantly elevated in comparison with healthy controls (205.9±31.8 pg ml−1). The presence of IL-18 was also demonstrated in scales from skin lesions. Treatment caused a significant decrease of plasma IL-18 concentration to 250.2±13.8 pg ml−1. There was a significant correlation between plasma IL-18 levels and PASI values (r=0.554). There was no correlation between IL-18 concentration in scales and PASI, between IL-18 concentrations in plasma and scales, and between plasma IL-18 and the disease duration or duration of present relapse. Plasma TGF-β1 concentration demonstrated a significant correlation with PASI (r=0.353), but not with IL-18 levels in plasma (r=0.063) and scales (0.141). The sum of plasma levels of IL-18 and TGF-β1 divided by the optimal coefficient demonstrated a statistically significant correlation with the highest r-value. The findings confirm an association between plasma IL-18 concentration and psoriasis severity. Moreover, it was shown that combined measurement of IL-18 and TGF-β1 in plasma can be considered as a possible biomarker of psoriasis activity.

Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales.

Vascular endothelial growth factor (VEGF) demonstrating pro-angiogenic activity promote new blood vessel formation in psoriatic lesions. The aim of this study was to evaluate the serum concentrations of VEGF, its soluble receptors (sVEGF R1 and R2) and VEGF content in scales of patients with psoriasis. To analyze possible association with activity of the disease, serum and scales from plaques were collected from 59 patients with exacerbated chronic plaque-type psoriasis. Mean concentrations of VEGF and sVEGF R1 in sera of patients were respectively two and four times higher than in healthy controls. Serum VEGF and sVEGF R1, but not sVEGF R2 demonstrated significant correlation with psoriasis area and severity index (PASI). There was also significant correlation between VEGF levels in serum and scales. Serum sVEGF R1 concentration was significantly elevated even in patients with low psoriasis activity (PASI<10), whereas increase of serum VEGF became significant in patients with medium activity (PASI: 10-20). Levels of serum VEGF and sVEGF R1 were the highest in patients with PASI>20. We confirmed association of both serum and scales VEGF concentrations with degree of psoriasis activity and demonstrated predominant increase of sVEGF R1 vs. VEGF in serum of patients with low psoriasis activity.

Effect of psoriasis therapy on VEGF and its soluble receptors serum concentrations

Backgroundu2002 Vascular endothelial growth factor (VEGF) is recognized a pivotal pro‐angiogenic factor responsible for new blood vessels formation in psoriatic lesion.

Albinterferon-alfa 2b: a new treatment option for hepatitis C.

Importance of the field: HCV infection affects 180 million people worldwide. Standard therapy combines weekly injections of pegIFN and daily ribavirin (RBV). Albinterferon (albIFN)-α2b is the most advanced in the development of an IFN-based compound. Areas covered in this review: The rationale for albIFN-α2b is to combine IFN-α antiviral activity with prolonged presence of human serum albumin in human blood. Initial experimental studies on albIFN-α2b were published in 2002. This review provides results of preclinical and subsequent clinical trials. Results of two Phase III clinical trials were presented in 2009 and will be published shortly. What the reader will gain: This review discusses the current status of knowledge on the efficacy and safety of albIFN-α2b. Phase III clinical trials demonstrated comparable efficacy of albIFN-α2b given every 2 weeks to weekly pegIFN-α2a, both in combination with RBV. However, the most promising seems to be every 4 weeks dosage. Take home message: Treatment with albIFN-α2b combined with RBV can provide comparable efficacy with the current standard of care medication with a reduced number of injections. Lower frequency of some adverse events and improved quality of life can be expected in patients receiving albIFN-α2b every 4 weeks.

Effect of psoriasis activity on serum adiponectin and leptin levels

Introduction Psoriasis is an inflammatory and chronic skin disease associated with obesity, cardiovascular diseases, diabetes and metabolic syndrome. Adipokines, as bioactive substances secreted from adipose tissue, are involved in various metabolic diseases. Aim To investigate the association between psoriasis severity and serum adiponectin and leptin levels in patients with psoriasis. Material and methods Serum fasting adiponectin and leptin levels were examined by an enzyme-linked immunosorbent assay in 49 patients with relapse of plaque-type psoriasis and 16 healthy controls. The results were correlated with the Psoriasis Area and Severity Index (PASI), body mass index (BMI), several inflammatory markers, duration of the disease and present relapse. Results Serum adiponectin and leptin levels were significantly decreased in psoriatic patients in comparison to the control group. There were no correlations between the above measures and PASI scores, patients’ age, duration of the disease, present relapse and hospitalization, neither between white blood cells or platelets counts. Serum adiponectin levels significantly correlated with C-reactive protein (CRP) levels. Adiponectin was negatively and leptin positively correlated to BMI at statistical significance. Multivariate analysis demonstrated a significant positive correlation between adiponectin and CRP or PASI concentrations as well as between BMI and leptin concentration. Conclusions The data showed that serum adiponectin levels increase and serum leptin levels decrease with psoriasis severity. Leptin might be useful in assessing severity and the risk of complications of psoriasis. Moreover, these results confirmed the relationship between leptin, obesity and psoriasis.

Serum adiponectin and leptin levels in psoriatic patients according to topical treatment

Abstract Objectives: Psoriasis has been considered as a systemic disease associated with obesity, cardiovascular diseases and metabolic syndrome. Adipokines have influence on many metabolic processes. Aim of this study was to evaluate the effect of conventional topical treatment on serum adiponectin and leptin levels in patients with psoriasis. Methods: Forty-nine patients with relapse of plaque-type psoriasis and 16 healthy controls were examined. Blood samples were collected before therapy and after 14 days of application. Serum adiponectin and leptin concentrations were examined by enzyme-linked immunosorbent assay for correlations with effectiveness of topical treatment. Results: Adiponectin and leptin serum levels were significantly decreased in psoriatic patients in comparison to the controls. As a result of the topical treatment, serum adiponectin level did not significantly change. Serum leptin level increased significantly, still remaining lower than in the controls. Conclusions: Leptin might be a useful marker in assessing the efficacy of the treatment for psoriasis.

Effect of Psoriasis Activity on Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 in Plasma and Lesional Scales

The aim of this study was to evaluate the association between psoriasis severity and concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in plasma and scales from psoriatic lesions, measured with an enzyme immunoassay in 24 patients and analysed with respect to psoriasis area and severity index (PASI). The mean plasma concentrations of both proteins in psoriatic patients significantly exceeded the control values. The proteins were also detectable in scales. There was a significant correlation between plasma MMP-1 concentration and the disease duration. The PASI values showed significant positive correlation with plasma TIMP-1 and significant negative correlation with MMP-1 content in scales. The highest plasma MMP-1 concentration was observed in patients with mild forms whereas the highest plasma TIMP-1 concentrations were demonstrated in severe forms of psoriasis. Our results confirm the role of these proteins in pathogenesis of psoriasis. In severe forms, a decrease in both MMP-1 and TIMP-1 was observed in scales, suggesting their insufficient tissue expression, which can be a crucial element of psoriasis aggravation.