LAUSR

Background: Adipokines, such as adiponectin, leptin, resistin and visfatin, are cytokines produced by the adipose tissue and involved in metabolism and inflammation1. Adiponectin is elevated in both serum and synovial fluid of subjects with rheumatoid arthritis (RA), suggesting a possible role of this adipokine in the pathogenesis of RA 2,3. Circulating levels of leptin, resistin, and visfatin are also higher in subjects with RA compared to controls 2,4. Objectives: Aim of this study was to determine if adiponectin, leptin, resistin, and visfatin predict the development of RA. Methods: Two nested-case control studies were performed including pre-symptomatic participants of two cohorts from Sweden: the Swedish Obese Subjects (SOS) study and a cohort of individuals identified within the Medical Biobank of northern Sweden. The SOS is a clinical trial including 4047 subjects with obesity6. During a follow-up for up to 29 years, 92 subjects developed RA. Among those 92 subjects, 82 subjects with available serum at baseline were matched 1:5 with 410 subjects who did not develop RA during follow-up. Matching was based on baseline age, sex, body-mass index (BMI), bariatric surgery yes/no, year of inclusion, and smoking. A nested case-control study of 88 sex- and age-matched pairs was performed within the Medical Biobank of Northern Sweden using blood samples donated before the onset of the first RA symptoms. The pre-dating time before onset of symptoms of RA was 8.5±5.0 years7. Baseline serum levels of adiponectin, leptin, resistin, and visfatin were measured using the Quantikine ELISA kit from R&D Systems (Wiesbaden, Germany). Visfatin could not be measured in the Biobank cohort, due to lack of serum. Both binary logistic as well as conditional logistic regression analyses were used to determine if adipokines were elevated years before the onset of RA. Results: In a multivariable analysis including adiponectin, leptin, resistin, visfatin performed in the SOS cohort, serum adiponectin was associated with a higher risk for RA independently of other adipokines (Odds ratio, OR, 1.1, 95% confidence interval, CI, 1.0-1.1, p value=0.01). Leptin, resistin and visfatin levels were not associated with the risk of RA. In the Biobank cohort, no association between adipokines and risk for RA was detected. However, when stratifying the population according to BMI, in the subgroup having BMI>25 (n=109), adiponectin levels were associated with higher risk for RA (OR 1.2, 95% CI 1.0-1.36, p=0.03), independently of leptin and resistin levels. Virtually the same results were obtained in both the SOS and the Biobank cohorts when conditional logistic regression analysis was used. Conclusion: Our results suggest that higher serum adiponectin levels predict the development of RA in subjects with overweight/obesity. References: [1] Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne) 2013;4:71. [2] Otero M, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1198-201. [3] Fantuzzi G. Adiponectin in inflammatory and immune-mediated diseases. Cytokine 2013;64:1-10. [4] Huang Q, et al. Serum resistin levels in patients with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Clin Rheumatol 2015;34:1713-20. [5] Sjöström L, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741-52. [6] Johansson L, et al. Antibodies directed against endogenous and exogenous citrullinated antigens pre-date the onset of rheumatoid arthritis. Arthritis Res Ther 2016;18:127. Disclosure of Interests: Yuan Zhang: None declared, Linda Johansson: None declared, Anna Rudin Grant/research support from: I have received research grants från AstraZeneca (2017-2018), Consultant for: I was paid consultant för AstraZeneca (2015-2018), Lena Carlsson Consultant for: I have received lecture fees from AstraZeneca, MSD and Johnson&Johnson, Solbritt Rantapää Dahlqvist Consultant for: Member of the advisory board, Lipum AB, Umeå, Sweden., Cristina Maglio: None declared