Background Metastasis-inducing S100A4 protein was identified as a pro-inflammatory and pro-destructive factor in rheumatoid arthritis (RA). Our research group has previously demonstrated that S100A4 is significantly elevated in peripheral blood, synovial fluid and synovial tissue of RA patients and that the levels of S100A4 correlate with disease activity.
Objectives To evaluate the levels of S100A4 in serum of patients with recent-onset RA and to characterize the association of S100A4 with disease activity and response to treatment.
Methods Serum levels of S100A4 protein were measured by ELISA in 59 patients with recent-onset RA (symptom duration <6 months) before and 3 months after initiation of treatment with disease-modifying antirheumatic drugs, and cross-sectionally in 42 healthy controls. IgM rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide antibodies (ACPA) and C-reactive protein (CRP) were analysed at baseline. Clinical disease activity (DAS28) was assessed at baseline and at 3, 6 and 12 months after initiation of treatment. The degree of radiographic joint damage was calculated from x-rays using the Sharp-van der Heijde Score (SHS) at baseline and at month 12.
Results Mean DAS28 (SD) significantly decreased from 5.36 (1.42) at baseline to 3.09 (1.52) at month 3 (n=59) and to 2.69 (1.19) at month 12 (n=40), respectively (p<0.0001). Of the 40 patients with available radiographs, 9 (23%) showed an increase in SHS (SHS >0) after 12 months. The levels of serum S100A4 protein were significantly higher in patients with recent-onset RA compared to healthy controls (646.60±602.60 vs. 46.97±30.12 ng/ml; p<0.001) and significantly decreased after 3 months of treatment (to 388.10±521.00; p<0.001). There was positive correlation of baseline levels of S100A4 with IgM-RF (r=0.611; p<0.0001) and ACPA levels (r=0.471; p<0.001). After adjustment for IgM-RF, the levels of S100A4 at baseline (r=0.403; p<0.05) as well as at month 3 (r=0.548; p<0.01) were positively correlated with DAS28 after 12 months of treatment in female patients (n=28). There was no correlation in male patients. The levels of S100A4 did not correlate with disease activity at baseline or with the change of disease activity over time. Furthermore, there was no association between baseline levels or changes of SA100A4 and achievement of DAS28 remission or radiographic progression.
Conclusions Our results indicate that circulating S100A4 levels are significantly higher in patients with recent-onset RA compared to healthy individuals and that higher S100A4 levels at baseline or at month 3 might have predictive potential for worse treatment response at month 12, at least in female patients with recent-onset RA.
Supported by The Charles University Grant agency - project No. 323011
Disclosure of Interest None Declared