Endothelin-1, α-Klotho, 25(OH) Vit D levels and severity of disease in scleroderma patients

Abstract

Considering the role of endothelin-1 (ET-1) in tissue remodeling and fibrosis during the development of scleroderma as well as the effect of α-Klotho in pathogenesis of calcinosis and/or endothelial cell injury and its correlation with severity of disease, this study aimed to evaluate serum ET-1, α-Klotho and 25(OH) vitamin D levels in patients with limited and diffuse scleroderma compared to healthy subjects. In this cross-sectional study, 60 scleroderma patients according to the ACR/EULAR 2013 criteria and 60 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and Medsger severity scale was assessed. Serum ET-1, soluble α-Klotho and 25(OH)D levels were measured using ELISA kits. The mean ± SD age of patients and controls was 46.2 ± 9.6 and 47.2 ± 7.0 years, respectively. Compared to healthy controls, serum ET-1 was significantly higher in SSc patients (p = 0.001); whilst serum α-Klotho and 25(OH)D were significantly lower in patients (p = 0.001). The most common organs involved in patients were skin, lung, peripheral vascular and gastrointestinal system and the severity of involvement was mainly mild and/or moderate. There were no significant differences in serum ET-1 and α-Klotho levels according to the severity of different organ involvement (p > 0.05). There was no significant correlation between presence or absence of calcinosis and negative or positivity of auto-antibodies with ET-1, α-Klotho and 25(OH)D levels. Although our study revealed higher serum ET-1 and lower serum α-Klotho levels in SSc patients compared to healthy controls, there were not any significant correlations between their serum levels with severity of organ involvement.

Association of endothelin-1 and cell surface adhesion molecules levels in patients with systemic sclerosis

“…Twenty five subjects in our study had elevated serum ET-1 concentration above the reference mean value (<0.65 pg/mL). This increase in ET-1 concentration during SSc can lead to skin thickening, fibrosis and vascular damage [10]. Other studies like the one conducted in 2013 also showed that in patients with SSc, ET-1 levels were higher than in control group [11].…”

Sirtuins and Accelerated Aging in Scleroderma

“…Siglecs, sialic acid-binding immunoglobulin-like receptors expressed by immune cells, block pro-inflammatory cascades and when deficient in mice, result in increased oxidative damage, reduced lifespan, and premature aging phenotypes [27]. Mice deficient in the protein klotho show signs of premature aging [38], and serum klotho levels were recently shown to be significantly lower in patients with SSc compared to age-matched controls [39, 40]. …”

Fibroblast Growth Factor 23 to Alpha-Klotho Index Correlates with Systemic Sclerosis Activity: A Proposal for Novel Disease Activity Marker

“…α-Klotho is a co-receptor for physiological FGF23 signaling and appears essential for FGF23-mediated regulation of mineral metabolism, including phosphate homeostasis. Patients with SSc are characterized by lower Klotho concentration [16,17,18,19]; however, the role of this finding remains obscure, as, in studies, Klotho was neither correlated with disease severity nor scleroderma-related damage. The aim of this study was to assess the simultaneous role of FGF23 and α-Klotho in the development of internal organ involvement in patients with the diffuse type of systemic sclerosis.…”