Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals.

Karen I Maijer,Ivy Y K Choi,Paul P Tak,Maria J H De Hair,Daniël A C A D Drop,Daniëlle M Gerlag,Elena Neumann,Ulf Müller-Ladner,Tamara H Ramwadhdoebe,Oliver Frey

doi:10.1371/journal.pone.0144932

Karen I Maijer, Ivy Y K Choi + Show 8 more

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https://doi.org/10.1371/journal.pone.0144932

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Abstract

ObjectivesWe have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA.MethodsFifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.ResultsThe development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.ConclusionsIn this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals.

Highlights

Rheumatoid arthritis (RA) is a systemic autoimmune disease, characterized by synovial inflammation in multiple joints leading to joint damage and disability
Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry
The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5; p = 0.020), after adjustment for overweight (HR1.7; p = 0.016)

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic autoimmune disease, characterized by synovial inflammation in multiple joints leading to joint damage and disability. During recent years the incidence of RA has increased [1, 2] The cause of this increase is not known, but it appears likely that environmental or life style factors account for this increase in a relatively short period of time. As the prevalence of obesity has increased dramatically, obesity may be an important life style risk factor in the development of RA [3]. We found in a prospective study in autoantibody positive subjects at risk of developing RA that after a median of 27 months follow up the overall arthritis risk was increased from 28% to 60% in individuals with a smoking history combined with overweight [7]. The identification of obesity as a risk factor for the development of RA was supported by a larger prospective study [8]

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