Comparative Serum Proteomic Analysis of Differentially Regulated Proteins in Patients with Rheumatoid Arthritis and Healthy Volunteers

Background: To identify differentially regulated serum proteins, we compared proteome profiles of sera from patients with rheumatoid arthritis (RA) and healthy controls using proteomics. Methods: Sera were collected from 43 patients with RA and 48 healthy volunteers. The samples were cleared of the most abundant major proteins by immunoaffinity chromatography. Serum protein profiles between the two groups were compared by two-dimensional differential gel electrophoresis (2D-DIGE) and differentially regulated proteins were studied using mass spectrometry. Results: We identified 26 differentially expressed serum proteins between patients with RA and healthy controls. A quantitatively significant change of protein levels was defined as at least 1.5-fold upregulation or 0.6-fold downregulation respectively. Using these criteria, patients with RA exhibited significantly higher levels of leucine-rich alpha-2-glycoprotein (p<0.01), apolipoprotein A-IV (p<0.001), clusterin (p<0.001), haptoglobin (p<0.001), Ig alpha-1 chain C region (p<0.05), retinol-binding protein 4 (p<0.001), serum amyloid A (p<0.01) and alpha-1-antichymotrypsin (p<0.01). The levels of serotransferrin were significantly decreased in RA patients (p<0.01). Conclusion: We identified eight proteins with significantly increased and one protein with significantly decreased serum levels in RA patients compared to healthy controls. Several of these proteins may be implicated in the pathogenesis of RA and may have potential in diagnostics and activity assessment of RA.