Expression of the peptide C4b-binding protein beta (C4BP& [beta]) in the arthritic joint

Olga Sánchez-Pernaute ^1*, Jorge Esparza-Gordillo ², Raquel Largo ³, Emilio Calvo ³, Mª Angeles Alvarez Soria ³, Mª Esther Marcos ⁴, Gabriel Herrero Beaumont ⁵ and Santiago Rodriguez de Cordoba ⁶

¹ Fundacion Jimenez Díaz, Spain
² Centro de Investigaciones Biológicas (CSIC), Spain
³ Fundación Jimenez Díaz, Spain
⁴ Fundacion Jimenez Diaz, Spain
⁵ Fundación Jimenez Diaz, Spain
⁶ Centro de Investigaciones Biologicas (CSIC), Spain

^* To whom correspondence should be addressed. E-mail: osanchez{at}fjd.es.

Accepted 23 April 2006

Abstract

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 C4BPápolypeptide, while the C4BPâpolypeptide inactivates protein S, interfering with the anticoagulatory protein C-dependent pathway.

Objective: To investigate the expression of C4BPb in the rheumatoid joint.

Methods: Expression of C4BP was studied in synovial explants from patients with RA, osteoarthritis (OA) and healthy controls, using immunohistochemistry and in situ hybridization. C4BP isoforms and free C4BPâ were studied in synovial effusions from patients with RA, OA and microcrystalline arthritis (MCA) by immunoblotting and total and free protein S levels by EIA.

Results: C4BPâ was over-expressed in the rheumatoid synovial membranes, in close association to the severity of synovitis and to the extension of interstitial fibrin deposits. As many as 85% of RA fluids contained free C4BPâ, while this unusual polypeptide was present in 50% fluids from MCA and 40% fluids from OA patients. Free protein S at the effusions was pathologically reduced in RA and MCA, and remained between normal values in OA patients.

Conclusion: C4BPâ is expressed by the inflamed synovial tissue, where it could participate in processes of tissue remodelling associated to invasive growth.

Keywords: complement, fibrin, rheumatoid arthritis, synovial fibroblast, synovitis

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