Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis.
BACKGROUND
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.
Osborn
Teresia M
TM
Department of Rheumatology and Inflammation Research, University of Gothenburg, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden. tmagnuson@rics.bwh.harvard.edu
Verdrengh
Margareta
M
Stossel
Thomas P
TP
Tarkowski
Andrej
A
Bokarewa
Maria
M
D000199:Actins / Q000032:analysis / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood*; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D018260:Gelsolin / Q000032:analysis*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000032:analysis*; D013582:Synovial Fluid / Q000737:chemistry
D000199:Actins; D015415:Biomarkers; D018260:Gelsolin; D020033:Protein Isoforms