Background/Purpose . Obesity per se is a systemic, low-grade inflammatory state and the adipose tissue is an endocrine organ that releases bioactive substances, including pro-inflammatory cytokines, like TNFα and IL6 and specific adipokines. There are only few data about early RA (ERA), suggesting that obesity associates with disease outcomes. In this work we aimed to evaluate whether the body weight, and fat metabolic (PEDF-Pigment Epithelium-Derived Factor) and meta-inflammatory parameters (Chemerin), could be associated with the outcomes in terms of disease remission and treatment in ERA patients (symptoms duration <12 months). 

Methods . 164 ERA patients, treated according to a treat-to-target strategy, were enrolled. At each visit the ACR/EULAR core data set was registered. Baseline BMI was collected and baseline interleukin-6, PEDF and Chemerin plasma levels were evaluated by ELISA’s methods.

Results . Of the 164 ERA patients (75.9% female, age 55.4±14.6 years, 34.3% very ERA, 66.9% seropositive, baseline DAS 3.4±1.0), 75 (45.7%) were normal weight, 66 (40.2%) overweight and 23 (14.0%) obese. Overweight and obese patients showed a higher disease activity at baseline compared to normal-weight patients (DAS: 3.6±1.0 vs 3.3±0.9, p=0.02). At baseline, BMI values correlated with baseline PEDF (r=0.33, p<0.001) and chemerin (r=0.31, p<0.001) plasma levels. Moreover, chemerin plasma levels correlated with age (r=0.31, p<0.001), baseline inflammatory markers (IL-6: r=0.28, p<0.001; ESR: r=0.39, p<0.001, CRP: r=0.35, p<0.001), swollen joint count (r=0.26, p<0.001), tender joint count (r=0.23, p<0.001), HAQ (r=0.24, p=0.002), DAS (r=0.34, p<0.001), CDAI (r=0.28, p<0.001) and SDAI (r=0.32, p<0.001). On the other hand, PEDF plasma levels correlated only with age (r=0.35, p<0.001) and baseline inflammatory markers (ESR: r=0.17, p=0.03, CRP: r=0.22, p=0.01). At 6 and 12 months none of the patients had a significant reduction of body-weight. A significant reduction of the disease activity at 6 and 12 months follow-up was observed in the three subgroup of ERA patients (normal-weight, overweight and obese patients). In the same manner, circulating chemerin levels significantly decreased over time; conversely, the circulating levels of PEDF remained unchanged. These findings were observed both in patients reaching and not reaching remission at 12 months of follow up.

Fourteen obese RA patients (BMI 35.3±3.2) with an active disease (DAS 3.5±0.7) underwent a dietary regimen for weight loss for six months, with no change in RA treatment. At the sixth month, the mean reduction in percentage of BMI was 8.9±5.3% and the average percentage of DAS reduction was 46.8±20.2% (DAS T6: 1.8±0.6, p=0.01 with respect to DAS T0).

Conclusion . In ERA patients, PEDF and chemerin seem to be biomarkers of obesity and metaflammation, respectively. Chemerin seems to be linked to RA disease activity and to treatment response, irrespective of body weight category, supporting its dual role in inflammation and metabolism and providing a link between chronic inflammation and obesity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/metaflammation-pedf-and-chemerin-potential-systemic-factors-which-link-obesity-to-response-to-therapy-in-early-rheumatoid-arthritis-2/