Abstract

Background:Patients with rheumatic diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are at increased risk of developing dyslipidaemia and premature cardiovascular disease (CVD)(1).Objectives:To investigate the relationship between proinflammatory cytokines, microRNA, and lipid profile in patients with RA, AS, and PsA.Methods:A group of 65 patients (RA15/ AS25/ PsA25) with high disease activity (mean DAS28 5,98 / ASDAS-CRP 3,7/ DAPSA 38,5) and 25 healthy controls (HC) were compared. Lipid profile comprised triglycerides (TG), total cholesterol(TC), low (LDL), and high-density lipoprotein (HDL). Serum concentrations of IL-6, IL-21, IL-17, TNF and osteoprotegerine (OPG) were measured by commercially available enzyme-linked immunosorbent assays. Expression of miR-233-5p,miR-92-3p,miR-485-3p,miR-10b-5p,let-7d-5p, miR-26 -a-2-3p levels in sera was normalized to miR-16a internal control. The Mann-Whitney test was applied for intergroup comparison, the correlation was assessed using Spearman’s Rank test.Results:Patients with RA revealed mixed dyslipidemia (mean values:TC196; LDL 117; HDL, 48 TG; 124 mg/dl), PsA revealed hypertriglyceridemia (TC 175; LDL 100; HDL 50; TG137 mg/dl) and in AS no specific profile was found (TC 179; LDL98; HDL55; TG103 mg/dl). Higher expression of miR-485was observed in patients with PsA (4,8-fold) and AS (5,9-fold) compared to RA and HC groups (3,1 and 1,5-fold p=0,02). Similarly, miR-26a revealed higher expression in patients with PsA (28,4-fold) and AS (21,5-fold) than in RA and HC (3,5 and 2,9-fold p<0,00). PsA patients had higher expression of miR-146b than patients with RA, AS and HC (40,9-fold vs 12,6 vs 15,7 vs 3,4-fold p=0,002) and higher miR-10b (11,7 vs 1,4 vs 4,9 vs 1,7-fold p=0,004). Patients with RA showed higher expression of let7-d than patients with PsA, AS and HC (22-fold vs 1,8 vs 2,3 vs1,9 -fold p=0,002). In PsA miR-92b expression correlated negatively with HDL levels (r=-0,62 p=0,02) and positively with fasting glucose (r=0,71 p<0,00). TG levels negatively correlated with TNF (r=-0,47 p=0,01), IL-17 (r=-0,49 p=0,01) and OPG (r=-0,51 p=0,00) serum levels. Let-7d correlated negatively with TC (r=-0,58 p=0,03). In RA IL-21 positively correlated with LDL (r=0,71 p=0,00) and TC (r=0,75 p=0,001) concentrations. TG levels correlated positively with expressions of miR-92b (r=6,9 p=0,02) and miR-26a (r=0,69 p=0,03). In AS expression of let-7d was correlated positively with HDL (r=0,41 p=0,00) and TC (r=0,45 p=0,00) levels and negatively with ASDAS-CRP (r=-0,675 p=0,02) and CRP levels (r=-0,53 p=0,01). There were no significant differences in OPG, IL-21 concentrations or miR-146b, miR-92b,miR-233 expressions.Conclusion:Differences in proinflammatory profile in RA, PsA, and AS seem to be associated with different phenotypes of dyslipidemia. In PsA expression of miR-92b and higher levels of TNF, IL-17 and OPG are associated with altered lipid profile and hypertriglyceridemia. High activity of AS is associated with lowered expression of let-7d, possibly influencing TC and HDL levels. Therefore, measuring lipid profile in active disease might be misleading. In active RA increase of TC and LDL levels was associated with high IL-21 concentration, while hypertriglyceridemia with miR-92b and miR-26a expressions.

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