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Open Access Research article

Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis

Teresia M Osborn12*, Margareta Verdrengh1, Thomas P Stossel2, Andrej Tarkowski1 and Maria Bokarewa1

Author Affiliations

1 Department of Rheumatology and Inflammation Research, University of Gothenburg, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden

2 Translational Medicine Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA

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Arthritis Research & Therapy 2008, 10:R117  doi:10.1186/ar2520


See related editorial by DiNubile, http://arthritis-research.com/content/10/6/124

Published: 27 September 2008

Abstract

Introduction

Gelsolin is an intracellular actin-binding protein involved in cell shape changes, cell motility, and apoptosis. An extracellular gelsolin isoform, plasma gelsolin circulates in the blood of healthy individuals at a concentration of 200 ± 50 mg/L and has been suggested to be a key component of an extracellular actin-scavenging system during tissue damage. Levels of plasma gelsolin decrease during acute injury and inflammation, and administration of recombinant plasma gelsolin to animals improves outcomes following sepsis or burn injuries. In the present study, we investigated plasma gelsolin in patients with rheumatoid arthritis.

Methods

Circulating and intra-articular levels of plasma gelsolin were measured in 78 patients with rheumatoid arthritis using a functional (pyrene-actin nucleation) assay and compared with 62 age- and gender-matched healthy controls.

Results

Circulating plasma gelsolin levels were significantly lower in patients with rheumatoid arthritis compared with healthy controls (141 ± 32 versus 196 ± 40 mg/L, P = 0.0002). The patients' intra-articular plasma gelsolin levels were significantly lower than in the paired plasma samples (94 ± 24 versus 141 ± 32 mg/L, P = 0.0001). Actin was detected in the synovial fluids of all but four of the patients, and immunoprecipitation experiments identified gelsolin-actin complexes.

Conclusions

The plasma isoform of gelsolin is decreased in the plasma of patients with rheumatoid arthritis compared with healthy controls. The reduced plasma concentrations in combination with the presence of actin and gelsolin-actin complexes in synovial fluids suggest a local consumption of this potentially anti-inflammatory protein in the inflamed joint.