THU0117 Chemokine ccl18 enriched in synovial fluid is involved in joint destruction through promoting migration of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Y.-Q. Mo, G.-C. Zhang, J. Jing, J.-D. Ma, L. Dai
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> CC chemokine ligand 18 (CCL18) which is either constitutively expressed or induced in monocytes/macrophages and dendritic cells has been reported to be highly expressed in peripheral blood and synovial fluid of rheumatoid arthritis (RA) patients compared with healthy controls, indicating the possible role of CCL18 in the development and pathogenesis of RA. <h3>Objectives</h3> To explore the association of serum and synovial fluid CCL18 with clinical and radiographic outcome in RA patients and its potential effect on RA fibroblast-like synoviocytes (FLS). <h3>Methods</h3> Consecutive patients with active RA (DAS28-CRP&gt;2.6) were recruited. Synovial fluid was collected from inflamed joints if available. Demographic and clinical data were collected according to the 2017 EULAR recommendation. Serum and synovial fluid CCL18 was detected by ELISA. RA-FLS was cultured <i>in vitro</i> with RA synovial fluid and neutralising antibody to CCL18. Migration/invasion ability was analysed by Transwell assay. <h3>Results</h3> (1) Among 83 RA patients, age (median and IQR, similarly hereinafter) was 50 (41~58) years old and 65 patients (78%) were female, with median disease duration 36 (12~102) months, median DAS28-CRP 5.0 (4.6~6.1). (2) Serum CCL18 was 107 (80~126) ng/mL, which was significantly higher than healthy controls [n=25, 51 (29~70) ng/mL,<i> p</i>&lt;0.001, figure 1A]. Serum CCL18 correlated slightly but significantly with CRP (<i>r</i>=0.385, <i>p</i>&lt;0.001), ESR (<i>r</i>=0.239, p=0.03), PrGA (<i>r</i>=0.249, p=0.03), DAS28-CRP (<i>r</i>=0.368, p=0.001), DAS28-ESR (<i>r</i>=0.336, p=0.003), SDAI (<i>r</i>=0.360, p=0.001), CDAI (<i>r</i>=0.328, p=0.004) and HAQ (<i>r</i>=0.325, p=0.004). (3) Synovial fluid CCL18 of 31 patients was 719 (415~1271) ng/mL, which was significantly higher than corresponding serum level (Paired test, <i>p</i>&lt;0.001, figure 1A). Among them, 13 patients who were treated according to treat to target strategy received X-ray assessment of hand/wrist both at baseline and month 12. Six patients who had one-year radiographic progression (a change of the Sharp/van der Heijde modified sharp score ≥0.5 units) showed higher synovial fluid CCL18 than other 7 patients without radiographic progression [1481 (1244~2034) ng/mL vs. 458 (405~681) ng/mL, p=0.004, figure 1B). (4) When incubated with RA synovial fluid, the migration ability of RA-FLS was significantly increased; but this effect was inhibited by neutralising antibody to CCL18 (figure 1C). <h3>Conclusions</h3> CCL18 elevates especially in synovial fluid of RA patients, which may correlate with one-year radiographic progression through promoting migration of RA-FLS. <h3>Acknowledgements</h3> This work was supported by National Natural Science Foundation of China (grant no. 81671612, 81601427) and Natural Science Foundation of Guangdong Province (grant no. 2016A030313307, 2017A030313470). <h3>Disclosure of Interest</h3> None declared