Synovial fluid CD146 (MUC18), a marker for synovial membrane angiogenesis in rheumatoid arthritis

Objective. CD146 (MUC18/MCAM/S-Endo) is a marker of tumor progression and m etastasis formation in human melanoma. This molecule has also been identifi ed in smooth muscle, endothelial cells, and activated T lymphocytes. We mea sured the synovial fluid levels of soluble CD146 in various human joint dis eases, including rheumatoid arthritis (RA). In addition, we studied the dis tribution of CD146 in normal and RA synovial tissues. Methods. CD146 was isolated from MEL-OH melanoma cells and characterized by Coomassie blue staining and Western blotting. Soluble CD146 was measured b y competitive enzyme-linked immunosorbent assay in synovial fluids of 3 hea lthy individuals and 7 cadavers (controls), as wells as in patients with tr aumatic joint injury (n = 10), osteoarthritis (OA; n = 10), psoriatic arthr itis (PsA; n = 10), other non-PA polyarthritis (NRAP; n = 10), and RA (n = 31), Immunohistochemistry was performed on 3 normal and 3 RA synovial tissu es. Flow cytometric, reverse transcription-polymerase chain reaction, and W estern blot analyses were performed on enzymatically separated RA synovial tissue cells. Results. Compared with controls (mean a SD 10 +/- 2 ng/ml), significantly e levated synovial fluid levels of soluble CD146 were detected in patients wi th OA, PsA, and RA (17 +/- 7, 21 +/- 11, and 39 +/- 16 ng/ml, respectively; P < 0.02-0.001), but not in patients with traumatic joint injury or NRAP. Patients with early RA (<1 year after diagnosis) revealed the highest level s (51 +/- 15 ng/ml, n = 10; P < 0.001 versus controls). In RAI soluble CD14 6 correlated significantly with morning stiffness (P < 0.001), the number o f tender joints (P < 0.02), and the number of swollen joints (P < 0.005), b ut not with the erythrocyte sedimentation rate (P = 0.07) or the C-reactive protein level (P = 0.57). Conclusion. Since CD146 is expressed almost exclusively by vascular endothe lium, high levels of soluble CD146 found in RA synovial fluid, particularly in patients with early disease, could reflect increased activity of endoth elial cells and angiogenesis.