Serum-soluble folate receptor β as a biomarker for the activity of rheumatoid arthritis synovitis and the response to anti-TNF agents

This study aims to develop a sandwich ELISA system for the measurement of soluble folate receptor β (sFRβ) and evaluate whether base line levels of serum sFRβ are a biomarker for the activity of RA synovitis and the response to anti-TNF agents. Serum sFRβ from normal controls (41 samples), patients with OA (29 samples), and patients with RA (27 samples) and synovial fluid sFRβ from patients with RA (17 samples) were measured by sandwich ELISA, using anti-FRαβ and anti-FRβ antibodies as capture and detection antibodies, respectively. Baseline levels of serum sFRβ before therapy were evaluated in relation with DAS28-CRP or CRP and response to anti-TNF agents at 3-month follow-up. sFRβ levels in RA synovial fluids were higher than those in RA sera, and sFRβ levels in RA sera were higher than those in osteoarthritis and normal control sera. A significant relationship was observed between serum sFRβ levels and the DAS28-CRP scores or CRP values. The area under curve (AUC) values for receiver-operating characteristic curves defined using the serum sFRβ levels of RA patients before therapy had a higher predictive capacity than DAS28-CRP and CRP for the effective response of anti-TNF agents. The high serum sFRβ levels with a cutoff value of 8 ng/mL were 100% specificity for the effective response of anti-TNF agents. The findings support that the serum sFRβ levels in patients with RA act as a disease activation biomarker and that high serum sFRβ levels act as a predictive biomarker for the response to anti-TNF agents.