Abstract
Objective: Obesity is a risk factor for Rheumatoid Arthritis (RA) being associated to low grade inflammation. This study aimed to determine whether PEDF and Chemerin are biomarkers of inflammation related to fat accumulation in RA and to investigate whether weight loss associates with clinical disease improvement through the modification of fat-related biomarkers in overweight/obese RA with low-moderate disease.Participants and Methods: Two-hundred and thirty RA patients were enrolled, of whom 176 at disease onset treated according to a treat-to-target strategy (T2T) and 54 overweight/obese RA in stable therapy and low-moderate disease activity. Gene expression of adipokines, interleukin-6 and their receptors were examined in adipose tissue from obese RA. Obese RA with low-moderate disease activity underwent low-calories diet aiming to Body Mass Index (BMI) reduction >5%, maintaining RA therapy unchanged. Chemerin, PEDF and Interleukin-6 plasma values were assessed by ELISA and disease activity was evaluated.Results: At RA onset, PEDF and Chemerin plasma values correlated with BMI (p < 0.001) but only Chemerin plasma values correlated with disease activity (p < 0.001). After adopting a T2T strategy, Chemerin arose as an independent factor associated with remission in early RA [OR(95%CIs):0.49(0.25–0.97)]. Moreover, after low-calories diet, RA with low-moderate disease activity reaching BMI reduction ≥5% (62.6%) at 6 months had significant decrease of PEDF (p < 0.05) and Chemerin (p < 0.05) plasma values, in parallel with the improvement in disease activity.Conclusions: PEDF and Chemerin arose as biomarkers of obesity and metaflammation respectively, providing a link between chronic inflammation and excess of body weight in RA. Therefore, BMI reduction of at least 5% in obese RA allowed better disease control without modifying RA treatment.
Highlights
Obesity is a risk factor for autoimmune diseases as Rheumatoid Arthritis (RA) [1,2,3] since adipose tissue releases adipokines able to create a low grade inflammatory environment [4,5,6,7,8]
To investigate whether specific molecules related to adipose tissue excess are associated with the inflammatory burden of RA, pigment epithelium derived factor (PEDF), and Chemerin plasma values were assessed in RA patients at disease onset compared to healthy subjects stratified by BMI category [30 healthy individuals, among whom 70% female, with a mean age of 50.0 years (SD = 9.6) and 12 (40.0%) overweight or obese]
PEDF and Chemerin plasma values were similar in ERA patients at diagnosis (PEDF: 13.1 ± 3.9 μg/ml, Chemerin: 108.6 ± 52.2 ng/ml) and controls (PEDF: 13.7 ± 2.4 μg/ml; p = ns; Chemerin: 95.2 ± 34.1 ng/ml; p = ns), while IL-6 plasma values were significantly higher in ERA patients than in controls (20.3 ± 34.5 pg/ml vs. 1.6 ± 3.8 pg/ml; p < 0.001)
Summary
Obesity is a risk factor for autoimmune diseases as Rheumatoid Arthritis (RA) [1,2,3] since adipose tissue releases adipokines able to create a low grade inflammatory environment [4,5,6,7,8]. The link between obesity and RA is not fully clarified since there are no parameters available at the moment to understand the inflammation related to fat accumulation and the behavior of fat-inflammation under weight loss. Pigment epithelium derived factor (PEDF) is one of the most abundant proteins secreted during adipocytes maturation directly linked to central obesity [9,10,11,12]. Overweight and obese healthy subjects show higher Chemerin values than normal weight, whose plasma values decrease after diet [13, 14]. Despite Chemerin was found in inflamed tissues and biological fluids of RA, promoting synovial fibroblasts hyperplasia [15,16,17], it is not completely known whether Chemerin is associated with systemic inflammation or with adipose tissue activation in RA
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