Background Calgizzarin (S100A11) is a member of the S100 protein family that acts in many different tumors via regulating variety of biologic functions such as cell proliferation and inflammation.
Objectives To compare the expression of calgizzarin in synovial tissue, synovial fluid and serum between patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate its association with disease activity.
Methods Calgizzarin expression was analysed in synovial tissues from six patients with RA and six patients with OA by immunohistochemistry. Serum and synovial fluid calgizzarin levels were measured by ELISA in 43 patients with RA and 40 subjects with OA. Disease activity score based on 28 joints (DAS28-CRP) was used to assess disease activity. For in vitro experiments, peripheral blood mononuclear cells (PBMCs) were isolated from blood of patients with RA (n=3-9).
Results The expression of calgizzarin was significantly up-regulated in synovial lining as well as sublining layers in samples from patients with RA compared to those with OA. In agreement, serum (18.23±2.83 vs. 11.43±0.86 ng/ml; p=0.009) and particularly synovial fluid (280.35±38.84 vs. 55.50±10.92 ng/ml; p<0.0001) calgizzarin levels were significantly higher in patients with RA compared to OA. In addition, PBMCs from patients with RA spontaneously secreted higher levels of calgizzarin in comparison with OA (p=0.011) after 24 hours, and this secretion was enhanced by other S100 proteins, including S100A4 (p<0.001), S100A8 (p<0.01) and S100A9 (p<0.0001), but not by S100A12 (p=0.08). In patients with RA, synovial fluid calgizzarin levels correlated significantly with DAS28 (r=0.359, p=0.018), CRP (r=0.478, p=0.001), synovial fluid leucocyte count (r=0.662, p<0.0001) and serum anti-CCP levels (r=0.484, p=0.001), but not with IgM-RF levels (r=0.139, p=0.375). No such associations were observed for serum calgizzarin.
Conclusions Our data provide the first evidence of up-regulation of calgizzarin and its association with inflammation and disease activity in patients with RA.
Acknowledgements This study was supported by MHCR Research Project No. 00023728, Research Project SVV: 262512 and by IGA Research Project No. NT 13698-4
Disclosure of Interest None declared