Identification of proteins with increased expression in rheumatoid arthritis synovial tissues

J Rheumatol. 2009 May;36(5):872-80. doi: 10.3899/jrheum.080939. Epub 2009 Apr 15.

Abstract

Objective: A proteomic approach was applied to discover novel rheumatoid arthritis (RA)-specific proteins by comparing the expression profiles of synovial membranes from patients with RA, osteoarthritis (OA), and ankylosing spondylitis (AS).

Methods: Synovial tissues were collected from patients with RA (n = 10), OA (n = 10), or AS (n = 6), and healthy controls matched for age and sex. Proteins were separated by 2-dimensional polyacrylamide gel electrophoresis, and the proteins with significantly increased expression in the RA samples were subject to matrix-assisted laser adsorption-ionization time-of-flight spectrometry. Results were verified using Western blot and immunohistochemistry. Levels of the candidate proteins were measured within plasma and synovial fluids from the RA patients (n = 30), who had disease duration of 3-7 years, using ELISA. Levels were also measured within plasma from unmedicated RA patients (n = 41), who had disease duration of 1-6 months.

Results: Compared with the OA and AS tissue samples, the proteins Ig-kappa light-chain C region, PRDX4, SOD2, TPI, and TXNDC5 were found with increased expression in synovial tissues of RA patients. PRDX4, SOD2, TPI, and TXNDC5 had 2-fold or more increase in expression in some of the early RA plasma samples (58.55%, 31.7%, 26.8%, and 36.6%, respectively) as compared with the early OA samples and control samples. TXNDC5 had 2-fold or more increase in expression in 53.3% of blood samples and 73.3% of synovial fluid samples from patients with long disease duration of RA as compared with samples from OA and AS patients.

Conclusion: Functional classification indicated that these identified proteins were related with cell differentiation, glycol metabolism, immunoactivation, and endogenous antioxidant reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / metabolism
  • Blotting, Western
  • Female
  • Humans
  • Immunoglobulin kappa-Chains / analysis
  • Immunoglobulin kappa-Chains / metabolism
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Osteoarthritis / metabolism
  • Peptide Mapping*
  • Peroxiredoxins / analysis
  • Peroxiredoxins / metabolism
  • Protein Disulfide-Isomerases / analysis
  • Protein Disulfide-Isomerases / metabolism
  • Proteins / analysis
  • Proteins / metabolism*
  • Proteomics*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spondylitis, Ankylosing / metabolism
  • Superoxide Dismutase / analysis
  • Superoxide Dismutase / metabolism
  • Synovial Membrane / chemistry
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Triose-Phosphate Isomerase / analysis
  • Triose-Phosphate Isomerase / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Immunoglobulin kappa-Chains
  • Proteins
  • PRDX4 protein, human
  • Peroxiredoxins
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Triose-Phosphate Isomerase
  • Protein Disulfide-Isomerases
  • TXNDC5 protein, human