scholarly journals IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis

2022 ◽  
Vol 23 (1) ◽  
pp. 555
Author(s):  
Xing Wang ◽  
Hannah Kaiser ◽  
Amanda Kvist-Hansen ◽  
Benjamin D. McCauley ◽  
Lone Skov ◽  
...  

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10−12) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10−8). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10−5). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1–1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Bos ◽  
N.A Van Vliet ◽  
M Beekman ◽  
P.E Slagboom ◽  
M Vernooij ◽  
...  

Abstract Background/Introduction Increasing evidence shows that greater arterial calcification leads to an elevated risk of atherosclerotic cardiovascular disease. Risk factors and prognosis of arterial calcification seems to vary per site and between women and men. However, the underlying biological mechanisms of site-specific calcification and the associated sex differences are largely unknown. Within the BBMRI framework, we performed a multi-cohort study on the associations of the circulating levels of metabolic biomarkers with arterial calcification at various sites among women and men. Purpose To examine the associations of the circulating levels of metabolic biomarkers with coronary artery (CAC), aortic arch (AAC) and the aortic valve (AVC) calcifications among women and men. Methods We included a total of 1,114 participants from the population-based Rotterdam Study and 390 from the Leiden Longevity Study. Study populations were comparable concerning study characteristics. Blood samples were used to determine a wide range of plasma metabolic biomarkers by proton nuclear magnetic resonance (NMR). Participants underwent non-contrast computed tomography to quantify the volume of CAC, AAC, and AVC. Linear regression modelling adjusted for relevant covariates was used to assess the associations of 166 metabolic biomarkers with CAC, AAC, and AVC. Correction for multiple testing was based on 33 independent metabolic biomarkers (p-value 0.05/33 = 1.5 x 10–3). Results Mean (standard deviation - SD) age was 69.5 (6.8) and 780 (52.0%) of the study population were women. One SD increase in concentration of a1-acid glycoprotein, was associated with a 0.10 SD (standard error (SE) = 0.03) increase in AAC (p-value = 9.5x10–4) in the overall population (Figure 1). When we stratified our analyses based on sex, this association was mainly driven by men [beta (SE) per SD: 0.12 (0.05), p-value = 0.007]. Moreover, an SD increase in acetate was associated with a 0.14 SD (SE = 0.04) decrease in CAC (p-value 1.7x10–4) in women but not in men [beta (SE) per SD: −0.04 (0.03), p-value = 0.22] (Figure 1). Conclusion(s) Higher levels of circulating glycoproteins were associated with increased AAC in men. Moreover, lower levels of circulating acetate were associated with increased CAC in women. These results provide evidence for location-specific differences and sex-specific effects in the underlying biological mechanisms of atherosclerosis. Our findings carry the potential to contribute to the early detection of individuals at increased risk for developing atherosclerotic cardiovascular disease and to a better understanding of disease etiology. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was performed within the framework of the BBMRI Metabolomics Consortium funded by BBMRI-NL, a research infrastructure financed by the Dutch government through Netherlands Organisation for Scientific Research (NWO) (Grant Nos. 184.021.007 and 184033111). MK was supported by VENI grant (91616079) from The Netherlands Organization for Health Research and Development (ZonMw).


2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.


Author(s):  
Christian S. Bork ◽  
Søren Lundbye-Christensen ◽  
Stine K. Venø ◽  
Anne N. Lasota ◽  
Erik B. Schmidt ◽  
...  

2021 ◽  
Vol 23 (5) ◽  
Author(s):  
Alison L. Bailey ◽  
Saif Al-Adwan ◽  
Eliea Sneij ◽  
Nicholas Campbell ◽  
Matthew E. Wiisanen

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