Objective: To assess the potential of metastasin S100A4 as a biological marker in patients with RA.
Methods: A total of 87 unselected patients with established RA (disease duration 2-44 years) and treated with MTX and infliximab at a single rheumatology centre were included in a cross-sectional study. Radiographs of hands and feet were taken prior to infliximab treatment and at inclusion (time interval 48 ± 27 months) and scored for the radiographic damage. S100A4 levels were analysed in relation to radiographic damage, clinical disease activity (DAS-28), inflammation (IL-6, CRP, ESR), bone and cartilage markers [MMP-3, COMP, C-telopeptide of type I collagen (CTX-I)] and proto-oncogenes [survivin, insulin-like growth factor 1 (IGF-1), Flt3 ligand].
Results: High levels of S100A4 were associated with severe radiographic damage (OR = 3.40, P = 0.025), non-response to infliximab (OR = 4.63, P = 0.003), presence of antibodies to infliximab (OR = 6.24, P = 0.003) and high levels of Flt3 ligand (OR = 2.73, P = 0.04). Regression analysis showed that high S100A4 was predictive for radiographic progression during infliximab treatment [positive predictive value (PPV) 0.68, P = 0.05]. Low levels of S100A4 were associated with response to infliximab (OR = 2.67, P = 0.049), clinical remission (OR = 4.01, P = 0.0047) and negative RF (OR = 9.22, P = 0.0047). S100A4 correlated with survivin (r = 0.71, P > 0.0001).
Conclusion: S100A4 levels are increased in proportion to radiographic damage and its further progression in RA patients. High S100A4 levels were associated with a poor clinical response to infliximab and high rate of anti-infliximab antibodies. The finding of a correlation between S100A4 and survivin and Flt3 ligand suggests that these proteins may represent a new cluster of biomarkers predicting radiographic progression and poor treatment response in RA patients.