Expression of the peptide C4b-binding protein β in the arthritic joint

Background: C4b-binding protein (C4BP) is a plasma oligomeric glycoprotein that participates in the regulation of complement and haemostasis. Complement-regulatory activity depends on the C4BP alpha-polypeptide, whereas the C4BP beta-polypeptide inactivates protein S, interfering with the anti-coagulatory protein C-dependent pathway. Objective: To investigate the expression of C4BP beta in the rheumatoid joint. Methods: Expression of C4BP was studied in synovial explants from patients with rheumatoid arthritis, osteoarthritis and healthy controls, using immunohistochemistry and in situ hybridisation. C4BP isoforms and free C4BP beta were studied in synovial effusions from patients with rheumatoid arthritis, osteoarthritis and microcrystalline arthritis (MCA) by immunoblotting; total and free protein S levels were studied by enzyme immunoassay. Results: C4BP beta was overexpressed in the synovial membranes of patients with rheumatoid arthritis, in close association with the severity of synovitis and the extension of interstitial fibrin deposits. As many as 85% fluids from patients with rheumatoid arthritis contained free C4BPb, whereas this unusual polypeptide was present in 50% fluids from patients with MCA and 40% fluids from patients with osteoarthritis. Free protein S at the effusions was pathologically reduced in patients with rheumatoid arthrits and MCA, and remained normal in patients with osteoarthritis. Conclusion: C4BPb is expressed by the inflamed synovial tissue, where it can participate in processes of tissue remodelling associated with invasive growth.