[Aberrant over-expression of adenosine deaminase and its significance on rheumatoid arthritis]

Adenosine deaminase (ADA; EC 3.5.4.4) activity is elevated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Since the anti-inflammatory effect of methotrexate is reportedly associated with increased levels of extracellular adenosine, the study was undertaken to clarify the role of two ADA isozymes (ADA1 and ADA2) in the pathogenesis of RA. The activities of ADA1 and ADA2 were measured in SF from RA and osteoarthritis (OA) patients, sera from RA patients, and lysates prepared from mononuclear and polymorphonuclear cells from RA-SF, peripheral blood from RA patients, and fibroblast-like synoviocytes (FLS) from RA and OA patients. Also investigated were the effects of proinflammatory cytokines on ADA1 activity and ADA mRNA expression in RA-FLS by the real-time PCR assay. The adenosine concentration in RA-SF was determined using a radioimmunoassay. The adenosine concentration in RA-SF ranged from 0.027 microM to 0.508 microM (mean+/-SD, 0.156+/-0.132). At these concentrations, ADA1 is expected to be functionally dominant due to its higher affinity for adenosine. ADA1 activity in RA-SF (14.4+/- 8.5 IU/l) was significantly higher than in OA-SF(3.0+/- 1.1 IU/l) or RA-sera (3.0+/-0.6 IU/l), suggesting they are the major source of ADA1 in RA-SF. Proinflammatory cytokines failed to affect ADA1 activity or ADA mRNA expression in RA-FLS. Taken together, these findings suggest that the elevated ADA1 activity is an intrinsic characteristic of RA-FLS, which likely contributes to the pathogenesis of RA by neutralizing the anti-rheumatic properties of endogenous adenosine.