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Background: Adiponectin is an adipokine that circulates in blood in three main forms, low molecular weight trimers, middle molecular weight hexamers, and high molecular weight (HMW) multimers [1]. It is still unclear which form of adiponectin is the predominant one to mediate the protein functions. Total adiponectin levels are elevated in both serum and synovial fluid of patients with rheumatoid arthritis (RA) [2], and total circulating adiponectin levels associate with inflammatory markers in a population at high risk for future RA [3]. However, the association of circulating adiponectin with markers of disease activity in subjects with RA is still matter of debate.
Objectives: The aim of the study was to determine whether total and/or HMW adiponectin levels associate with markers of disease activity and/or plasma chemokine levels in a cohort of subjects with untreated early RA.
Methods: The cohort consisted of 70 untreated subjects with newly diagnosed RA. Clinical disease activity markers, including DAS28, CDAI, CRP and ESR, were assessed and data on patient history were recovered from clinical files. The plasma levels of 15 chemokines were measured with LEGENDplex™ Human Proinflammatory Chemokine Panel or ELISA, and total and HMW adiponectin plasma levels were determined with ELISA. Multivariate factor analysis was used to examine the association between total and HMW adiponectin plasma levels with clinical disease activity markers and plasma chemokine levels. The multivariate models were used to select potentially associated markers and chemokines, which were then tested with linear regression.
Results: Both total and HMW adiponectin levels were associated with several clinical markers of disease activity (CRP, ESR, DAS28-ESR). Total adiponectin levels were also associated with DAS28-CRP. Furthermore, a positive association was found between total adiponectin levels and the pro-inflammatory chemokines CXCL10, CXCL9, and CCL2, whereas HMW adiponectin levels only associated with CXCL9.
Conclusion: This study shows for the first time that both total and HMW adiponectin levels are associated with several markers of disease activity as well as pro-inflammatory chemokines in a well-characterized cohort of subjects with untreated early RA. Those findings indicate adiponectin as a potential disease marker in subjects with RA.
REFERENCES:
[1] Maeda N, Funahashi T, Matsuzawa Y, Shimomura I. Adiponectin, a unique adipocyte-derived factor beyond hormones. Atherosclerosis. 2019 Nov 2; 292:1-9.
[2] Lee YH, Bae SC. Circulating adiponectin and visfatin levels in rheumatoid arthritis and their correlation with disease activity: A meta-analysis. International journal of rheumatic diseases. 2018 Mar; 21(3):664-672.
[3] Hughes-Austin JM, Deane KD, Giles JT, Derber LA, Zerbe GO, Dabelea DM, et al. Plasma adiponectin levels are associated with circulating inflammatory cytokines in autoantibody positive first-degree relatives of rheumatoid arthritis patients. PLOS ONE. 2018; 13(6):e019957
Clinical parameters
| Characteristic | no=70 |
|---|---|
| Women, no (%) | 47 (69) |
| Age, yr | 55 (42-64) |
| BMI | 25 (23-28) |
| CRP, mg/L | 9 (4-31) |
| ESR, mm/hour | 24 (12-38) |
| SJC28 | 9 (5-12) |
| TJC28 | 9 (4-13) |
| DAS28-CRP | 5 (4-6) |
| DAS28-ESR | 5 (5-6) |
| ACPA+, no (%) | 57 (81%) |
| RF+, no (%) | 48 (69%) |
| CDAI | 28 (22-38) |
| Symptom Duration, months | 5 (3-8) |
| Smoking, no (%) | 8 (11%) |
Data shown as median (interquartile range), unless otherwise noted.
Abbreviations: BMI, Body-mass index; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; SJC28, swollen joint counts of 28; TJC28 tender joint counts of 28; DAS28, disease activity score in 28 joints; ACPA , Anti–citrullinated protein antibody; RF , Rheumatoid factor; CDAI , Clinical Disease Activity Index.
Linear regression analysis of total and HMW adiponectin with CRP Results are adjusted for sex, age and BMI
Linear regression analysis of total and HMW adiponectin with CXCL10 Results are adjusted for sex, age and BMI
Disclosure of Interests: Georgios K. Vasileiadis: None declared, Anna-Carin Lundell: None declared, Yuan Zhang: None declared, Anna Rudin Consultant of: Astra/Zeneca, Cristina Maglio: None declared