Myeloid-related protein (MRP) 8 and MRP 14 in rheumatoid arthritis and spondyloarthropathy

Background

Myeloid-related protein (MRP) 8 (S100A8) and MRP 14 (S100A9) are calcium-binding proteins belonging to the S100 family. Their expression in leukocytes is restricted to neutrophils and early differentiation stages of monocytes. In several inflammatory diseases, serum concentrations and expression of MRP 8 and MRP 14 by infiltrating myelomonocytic cells correlate with disease activity, indicating that both proteins are released during inflammatory processes.

Objective

To analyze MRP 8/14 concentrations in serum and synovial fluid (SF), and expression of MRP 8 and MRP 14 in synovial tissue in RA and SpA.

Methods

Paired serum, SF and synovial tissue samples of 20 RA and 20 SpA patients and sera of 20 healthy controls (HCs) were analyzed. Concentrations of MRP 8/14 in serum and SF were determined by ELISA. The expression of MRP 8 and MRP 14 in synovium was investigated using immunohistochemistry on frozen sections. Sections were scored on a semiquantitative 4-point scale. For statistical analysis, the Mann–Whitney test and Spearman's Rho correlations were performed. P values ≤ 0.05 were considered significant. Bonferroni corrections were applied when necessary.

Results

Serum concentrations of MRP 8/14 were significantly higher in RA (medians 1285 ng/ml [210–11390]) and SpA (medians 570 ng/ml [230–2730]) than in HCs (medians 280 ng/ml [130–680]) (RA versus HCs: P < 0.001; SpA versus HCs: P = 0.002). Moreover, MRP 8/14 serum concentrations in RA were increased, in comparison with SpA (P = 0.036). Also for SF concentrations, MRP 8/14 levels were significantly higher in RA than in SpA (medians 11,720 ng/ml [0–95,000] versus 2445 ng/ml [0–33,250], P = 0.049). MRP 8 staining in the lining layer was more prominent in RA than in SpA (medians 2 [0–3] versus 1 [0–3], P = 0.019), and MRP 14 staining in the sublining layer was more abundant in RA than in SpA (medians 2 [0–3] versus 1 [0–2], P = 0.026). In RA, MRP 8/14 concentrations in serum correlated well with SF concentrations (r = 0.650, P = 0.002).

Conclusion

We found significantly higher MRP 8 and 14 serum concentrations, MRP 8 and 14 SF concentrations, and MRP 8 and 14 expression in synovial tissue in RA than in SpA. In both diseases, MRP 8 and 14 serum levels were higher than in HCs.