Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints and infiltration by activated macrophages. TNFa is a central mediator in the process, leading to joint swelling and subsequent articular destruction. CD163 is a scavenger receptor expressed by M2C macrophages. We previously reported the soluble (s) form to be associated with disease activity and reflect discontinuation of anti-TNFa treatment in RA². The mannose receptor, CD206, is also a scavenger receptor, but expressed by M2A-macrophages and dendritic cells. It is involved in collagen internalization and degradation. The soluble form is suggested as biomarker of M2A-macrophage activation. In this study, we investigate sCD206 plasma levels in early RA patients, before, during and after anti-TNF_ treatment.

Methods: Plasma levels of sCD206 was measured by ELISA in samples from 155 early RA patients belonging to the OPERA cohort[1]. Age 53.5 years 70% females, average disease duration: 3 months. Patients were randomized to 12 months conventional methotrexate and placebo (PLA) or methotrexate and adalimumab (ADA) treatment, followed by open-label treatment with DMARD and if needed adalimumab. The disease was assessed at baseline and after 3, 6, 12 and 24 months by: Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ), C-Reactive Protein (CRP), Swollen Joint Counts (SJC40), Tender Joint Counts (TJC40), Clinical Disease Activity Index (CDAI), Visual Analogue Scale (VAS) for pain, IgM-RF and anti-CCP. Statistical analysis was performed by studentÕs t-test, SpearmanÕs Rank correlation and linear regression.

Results: Baseline plasma level of sCD206 in treatment na•ve RA patients was 0.33 mg/l (CI: 0.33 mg/l Ð 0.38 mg/l) corresponding to the upper part of the reference interval for healthy controls (0.10 mg/l Ð 0.43 mg/l). Anti-TNFa treatment significantly decreased plasma sCD206, whereas discontinuation of anti-TNFa resulted in increasing sCD206 plasma levels. In the PLA group, sCD206 levels was decreased after 3 months, and did not differ from those at baseline after 6 months. In the ADA group, however, levels remained lower than baseline throughout the treatment period (Figure 1). Soluble CD206 correlated with previously measured sCD163[2] at all 5 time points (r²: 0.24-0.38, p<0.001). Soluble CD206 did not correlate with clinical nor biochemical disease markers, however sCD206 increased when adalimumab was discontinued.

Conclusion: Plasma sCD206 decreased with treatment in early RA patients. Treatment with anti-TNFa preserved this decrease in the entire follow-up period; however, discontinuation of anti-TNFa was reflected by increasing sCD206 plasma levels. Soluble CD206 did not reflect disease activity in early RA, but like sCD163, reflected anti-TNFa treatment. Figure 1