Expression of chemokines and their receptors in synovial tissue of patients with rheumatoid arthritis, osteoarthritis and reactive arthritis

Background

Chemokine receptors and their ligands play a crucial role in the recruitment of leukocyte subsets into inflamed tissue. Their exact expression in synovial tissue (ST) of patients with various forms of arthritis has yet to be determined.

Objective

The objective of this study was to determine the expression of an extensive number of chemokines and their receptors in patients with rheumatoid arthritis (RA) and other forms of arthritis.

Methods

Synovial biopsies were obtained with a Parker-Pearson needle from patients with RA (n = 23), osteoarthritis (OA) (n = 16), and reactive arthritis (ReA) (n = 8). ST was studied in patients with both early and late stages of disease. Sections were analyzed by immunohistochemistry using monoclonal antibodies against CD3 (T-cells), CD68 (macrophages), CD13 (aminopeptidase N), CCR1, CCR2b, CCR5, CXCR4, CCL2 (MCP-1), CCL8 (MCP-2), CCL7 (MCP-3), CCL14 (hCC-1), CCL15 (hCC-2), CCL16 (hCC-4), and CCL5 (RANTES). Digital image analysis was used to quantify the staining and for statistical analysis the Kruskal-Wallis H test and the Mann–Whitney U test were used.

Results

All chemokines and chemokine receptors were detected in inflamed synovium. There was abundant expression of especially CD13, CCR1, CXCR4, CCR5, CCL7, and CCL8 in all forms of arthritis. The ligands CCL7, CCL8, CCL14, CCL15, and CCL16, which have not previously been described in ST, were all expressed in inflamed ST. The expression of CCL5 (RA, 11182 ± 2239 (mean integrated optical density ± SEM); OA, 8759 ± 2930; ReA, 2081 ± 1181; P = 0.010) and CCL15 (RA, 4993 ± 1601 (mean integrated optical density ± SEM); OA, 1738 ± 573; ReA, 1252 ± 1919; P = 0.043) was significantly higher in rheumatoid ST compared with disease controls.

Conclusion

These results suggest a potentially important role for a variety of chemokines and their receptors in the migration of inflammatory cells towards the synovial compartment. Disruption of the chemokine network might represent a novel therapeutic approach in RA, but also in other arthritides.