Chemerin serum levels in systemic sclerosis: a novel marker of early and active disease?

Aim of the study. Systemic sclerosis (SSc, scleroderma) is a chronic systemic autoimmune disorder characterized by tissue fibrosis, microvasculopathy and immune activation. The excessive deposition of extracellular matrix is mediated by activated fibroblasts; the nuclear orphan peroxisome proliferator-activated receptor gamma (PPAR-) has been identified as a master negative regulator of fibroblast activation. PPAR- expression and activity has been shown to be impaired in scleroderma patients, being inversely related to transforming growth factor (TGF)- signaling in lesional tissues. Recently, PPAR- has been shown to induce chemerin expression and secretion in mesenchymal stem cells as well as in non-adipogenic cells. Chemerin, which is expressed mainly by epithelial cells and adipocytes, but also by chondrocytes and fibroblasts, belongs to the family of adipokines, a class of molecules involved in adipogenesis promotion. The working hypothesis of this study envisaged that chemerin expression might be impaired in SSc; the aim of this study was to test such hypothesis evaluating the serum levels of chemerin in a cohort of scleroderma patients. Materials and Methods. Fifty-five patients with a SSc diagnosis conforming to 2013 ACR/EULAR classification criteria (22 with diffuse cutaneous SSc [dcSSc] and 33 with limited cutaneous SSc [lcSSc]) were recruited. As controls, 15 patients with primary Raynaud’s phenomenon (RP) and 9 healthy subjects were included. The serum levels of chemerin were determined by a commercial ELISA assay (R&D Quantikine) following manufacturer instructions. The concentrations of chemerin were expressed in ng/ml. Statistical analysis was performed with STATA-10, p-values below 0.05 were considered statistically significant. Results. Scleroderma patients displayed higher chemerin serum levels as compared to healthy subjects, a difference which approached statistical significance (p=0.065), while subjects with SSc and those with RP presented similar chemerin levels. No significant difference in serum chemerin emerged between subjects carrying dcSSc and those with lcSSc nor subgrouping the patients upon the autoantibody profile. No significant relationship was found between chemerin and age. However, chemerin levels were found to significantly correlate with disease activity (p=0.0063, r=0.37). In particular, patients with a disease duration shorter than the median value of 48 months displayed significantly lower chemerin levels as compared to subjects with a longer disease duration (p=0.0008). When scleroderma patients were classified in four groups upon disease duration quartile values, chemerin values significantly predicted this classification at linear regression analysis (p=0.043, 95% CI 0.35-20.20). Conclusions. These data suggest that the serum levels of chemerin are reduced in the early and active stages of scleroderma, increasing once the disease progresses. Such findings support the potential involvement of chemerin in SSc, making future studies necessary to better understand its physiopathological role.