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Synovial fluid CD146 (MUC18), a marker for synovial membrane angiogenesis in rheumatoid arthritis
M Neidhart1, R Wehrli, P Brühlmann
1Center for Experimental Rheumatology, University Hospital, Zurich, Switzerland.
Objective:
CD146 (MUC18/MCAM/S-Endo) is a marker of tumor progression and metastasis formation in human melanoma. This molecule has also been identified in smooth muscle, endothelial cells, and activated T lymphocytes. We measured the synovial fluid levels of soluble CD146 in various human joint diseases, including rheumatoid arthritis (RA). In addition, we studied the distribution 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 by competitive enzyme-linked immunosorbent assay in synovial fluids of 3 healthy individuals and 7 cadavers (controls), as wells as in patients with traumatic joint injury (n = 10), osteoarthritis (OA; n = 10), psoriatic arthritis (PsA; n = 10), other non-RA polyarthritis (NRAP; n = 10), and RA (n = 31). Immunohistochemistry was performed on 3 normal and 3 RA synovial tissues. Flow cytometric, reverse transcription-polymerase chain reaction, and Western blot analyses were performed on enzymatically separated RA synovial tissue cells.
Results:
Compared with controls (mean +/- SD 10 +/- 2 ng/ml), significantly elevated synovial fluid levels of soluble CD146 were detected in patients with 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 levels (51 +/- 15 ng/ml, n = 10; P < 0.001 versus controls). In RA, soluble CD146 correlated significantly with morning stiffness (P < 0.001), the number of tender joints (P < 0.02), and the number of swollen joints (P < 0.005), but 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 endothelium, high levels of soluble CD146 found in RA synovial fluid, particularly in patients with early disease, could reflect increased activity of endothelial cells and angiogenesis.
Insights
Soluble CD146 levels are elevated in rheumatoid arthritis (RA) synovial fluid, correlating with disease activity. High levels in early RA suggest increased endothelial cell activity and angiogenesis.
Area of Science:
- Immunology
- Rheumatology
- Oncology
Background:
- CD146 (MUC18/MCAM/S-Endo) is a known marker for tumor progression and metastasis in melanoma.
- CD146 is also expressed in vascular endothelial cells, smooth muscle cells, and activated T lymphocytes.
Purpose of the Study:
- To measure soluble CD146 levels in synovial fluid across various human joint diseases, including rheumatoid arthritis (RA).
- To investigate the distribution of CD146 in normal and RA synovial tissues.
Main Methods:
- Soluble CD146 was quantified using competitive enzyme-linked immunosorbent assay (ELISA) in synovial fluid from controls and patients with traumatic joint injury, osteoarthritis (OA), psoriatic arthritis (PsA), other non-RA polyarthritis (NRAP), and RA.
- Immunohistochemistry was performed on synovial tissues. Flow cytometry, RT-PCR, and Western blot analyzed RA synovial tissue cells.
Main Results:
- Significantly elevated soluble CD146 levels were found in OA, PsA, and RA synovial fluid compared to controls.
- RA patients, especially those with early disease (<1 year diagnosis), exhibited the highest soluble CD146 levels.
- In RA, soluble CD146 correlated with morning stiffness, tender joint count, and swollen joint count.
Conclusions:
- High soluble CD146 levels in RA synovial fluid, particularly in early disease, may indicate heightened endothelial cell activity and angiogenesis.
- CD146's expression predominantly on vascular endothelium supports its role as a marker in inflammatory joint diseases.