Prevalence of anti-3-nitrotyrosine antibodies in the joint synovial fluid of patients with rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus

Abstract

Background: Increased reactive nitrogen species (RNS) production has been suggested in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis (OA) as well as in systemic lupus erythematosus (SLE). They are known to have direct toxicity to cells. High concentrations of serum nitrite/nitrate and elevated urinary nitrate:creatine ratio has been found in patients with RA, OA and SLE. Reactive nitrogen species play a role in the chronicity of inflammatory reaction such as cartilage and bone destruction seen in patients with RA and OA. Arthritis is also associated with increased intra-articular formation of 3-nitrotyrosine (3-NT), which may contribute to joint damage. There is growing evidence that nitrative injury plays an important role in oxidative stress in the etiology and pathogenesis of SLE. 3-nitrotyrosine is thought to be a relatively specific marker of nitrosative damage mediated by nitric oxide (NO) and its by-products.

Methods: Commercially available poly l-tyrosine was exposed to nitrating species resulting in the formation of 3-nitrotyrosine. Antibodies present in synovial fluid and sera of 30 patients with rheumatoid arthritis, 15 patients with osteoarthritis and 15 patients with SLE were studied for their recognition of 3-NT by direct binding ELISA.

Results: IgG from the synovial fluid (SF) of RA and OA patients, purified on protein A-Sepharose matrix, exhibited increased recognition of 3-NT, than the IgG isolated from the sera of RA and OA patients in competitive ELISA, whereas IgG isolated from the sera of SLE patients exhibited increased recognition of 3-NT, than the IgG isolated from the synovial fluid. There was a higher prevalence of antibodies against 3-NT in the synovial fluid than in the sera of patients with RA and OA. Higher level of anti-3-NT antibodies were found in the synovial fluid in the later stages of SLE when compared to the early stages but was not more than that found in the sera.

Conclusion: The RNS may be produced within the inflamed joints of RA and OA patients but not in SLE patients. The 3-NT levels also correlated directly with disease activity.