Background Obesity has been associated with an altered radiographic progression in rheumatoid arthritis (RA) and hand osteoarthritis (OA). While the underlying mechanisms of these associations remain unclear, it has become clear that adipose tissue secreted factors (adipokines) could play an important role in the systemic effects of obesity. Amongst them, adiponectin has been shown to influence joint damage. In RA patients, total adiponectin (totAPN) levels in serum associated positively with radiographic progression, suggesting an adverse effect on disease. Intruiguingly, high totAPN levels in serum of patients with hand OA (HOA) were associated with reduced relative risk for jointdamage progression, indicating a protective effect.
Adiponectin is a pleiotropic adipokine and consists of several isoforms in circulation: a trimeric low-molecular-weight adiponectin; a hexameric middle-molecular-weight adiponectin and a multimeric high-molecular-weight adiponectin (hmwAPN). Of the different adiponectin isoforms described, hmwAPN emerges as one of the most biologically active isoforms in circulation and its role in disease progression in RA and HOA remains unknown.
Objectives Here, we explored the possibility that the association between totAPN and disease progression in RA and OA is primarily mediated by the hmwAPN isoform.
Methods Concentrations of hmwAPN and totAPN were determined in baseline plasma of 324 RA patients selected from the Early Arthritis Cohort (EAC) and in baseline sera of 227 hand OA patients selected from the Genetics Arthrosis and Progression (GARP) study. The association between levels of hmwAPN and totAPN with radiographic progression were determined using a multivariate linear regression model (EAC cohort) or by generalized estimated equations (GARP cohort). Adjustments were made for age, gender, treatment strategy and Body Mass Index (BMI).
Results As reported previously, in RA patients totAPN associated positively with radiographic progression over 4 years (Sharp van der Heijde scores) (estimate 3.23, 95% CI (1.41 – 7.42)), whereas in patients with hand OA, totAPN associated negatively with radiographic progression (joint space narrowing (JSN)) (OR 0.37, 95%CI (0.18 – 0.78) tertile 2; OR 0.27 95%CI (0.12 – 0.64) tertile 3, compared to the lowest tertile). However, HmwAPN, did not associate significantly with radiographic progression in patients with HOA nor to RA, although in patients with RA we did observe a trend towards a positive association (estimate 1.53, 95%CI (0.97 – 2.4)) upon correcting for age, gender and treatment strategy. This trend was lost after further adjustment for BMI (estimate 1.29, 95%CI (0.79 – 2.11)). Similar results were obtained for RA patients when JSN was used as outcome measurement.
Conclusions Our data further substantiate the connection between APN-levels and radiographic progression in rheumatic disease and indicate that the association of totAPN with radiographic progression in RA and hand OA is not primarily mediated by (a selective effect of) hmwAPN.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.