leptin and Scleroderma--Limited

Adipose tissues secrete adipokines, peptides with potent effects modulating fibrosis, inflammation, and vascular homeostasis. Dysregulated adipose tissue biology and adipokine balance have recently been implicated in systemic sclerosis (SSc). This study was undertaken to determine whether altered circulating adipokine levels correlate with SSc disease subsets or clinical manifestations.. Multiplex assays were used to measure circulating adipokine levels in 198 patients with SSc and 33 healthy controls. Data were evaluated for correlations between serum adipokine levels and demographic and clinical features, including pulmonary arterial hypertension (PAH). To assess the relevance of adipsin, an adipokine involved in complement pathway activation, in SSc, we analyzed publicly available genetic and transcriptomic data.. Levels of adiponectin and adipsin differed significantly between controls and patients. Adipsin was significantly elevated in patients with limited cutaneous SSc (odds ratio [OR] 28.3 [95% confidence interval (95% CI) 7.0-113.8]; P < 0.0001), and its levels were associated with serum autoantibody status, pulmonary function and cardiovascular parameters, and PAH (OR 3.3 [95% CI 1.3-8.7]; P = 0.02). Elevated adipsin was more strongly associated with PAH than B-type natriuretic peptide was. Moreover, in SSc patients, adipsin gene single-nucleotide polymorphisms were associated with PAH. Transcriptome data set analysis demonstrated elevated adipsin expression in patients with SSc-related PAH.. We identify adipsin as a novel adipose tissue-derived marker of SSc-related PAH. Circulating adipsin levels might serve as predictive biomarkers in SSc. Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation and play an important role in the pathogenesis of SSc-related PAH.

Topics: Adiponectin; Adult; Aged; Autoantibodies; Complement Factor D; Cytokines; Female; Gene Expression Profiling; Humans; Hypertension, Pulmonary; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Nicotinamide Phosphoribosyltransferase; Odds Ratio; Polymorphism, Single Nucleotide; Resistin; Scleroderma, Diffuse; Scleroderma, Limited

Systemic sclerosis (SSc) is a chronic fibrotic collagen tissue disease. Leptin's role in regulating immune and inflammatory response has become increasingly evident. Resistin has pro-inflammatory properties and also is associated with inflammatory markers in some rheumatologic diseases. The purpose of this study was to determine serum leptin, resistin and tumor necrosis factor alpha (TNF-α) in SSc patients and evaluate their association with other frequently used laboratory and clinic findings.. Sixteen patients were compared with 30 healthy women of similar age and body mass index. Serum leptin, resistin and TNF-α levels were measured by enzyme-linked immunosorbent assay and results were assessed by Mann-Whitney U -test and Spearman's correlation test.. Leptin levels were significantly increased in the SSc group compared to controls (7789.43 ± 1180.72 pg/mL, 1790.55 ± 333.68 pg/mL, P < 0.0001). TNF-α was significantly elevated in patients and it was also positively correlated with leptin (25.30 ± 2.16 pg/mL, 20.95 ± 0.30 pg/mL, P = 0.001), (P = 0.002, r = 0.523). There was no association between leptin, resistin, TNF-α levels and skin score, activity score and disease duration in the SSc patients (P > 0.05).. Leptin, resistin and TNF-α levels were found to be higher in SSc in contrast to the control group. These adipokines may have differentiating roles in the pathogenesis of SSc. In order to verify these findings, further clinical studies are needed with larger patient groups.

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Female; Health Status; Humans; Leptin; Resistin; Scleroderma, Diffuse; Scleroderma, Limited; Severity of Illness Index; Skin; Tumor Necrosis Factor-alpha