Identification of Proteins with Increased Expression in Rheumatoid Arthritis Synovial Tissues

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. (First Release April 15 2009; J Rheumatol 2009;36:872-80; doi: 10.3899/jrheum.080939)