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Objective. Adenosine deaminase (ADA; EC 3.5.4.4) activity is elevated in the synovial fluid (SF) of patients with rheumatoid arthritis (RA). Since the antiinflammatory effect of methotrexate is reportedly associated with increased levels of extracellular adenosine, the present study was undertaken to clarify the role of 2 ADA isozymes, ADA1 and ADA2, in the pathogenesis of RA.Methods. The activities of ADA1 and ADA2 were measured in SF from RA and osteoarthritis (OA) patients, in sera from RA patients, and in lysates prepared from mononuclear and polymorphonuclear cells from SF from RA patients, peripheral blood from RA patients, and fibroblast-like synoviocytes (FLS) from RA and OA patients. Also measured were the effects of proinflammatory cytokines on ADA1 activity and ADA messenger RNA (mRNA) expression in RA FLS, as determined using real-time polymerase chain reaction. The adenosine concentration in RA SF was measured by radioimmunoassay.Results. The adenosine concentration in RA SF ranged from 0.027 M to 0.508 M (mean ؎ SD 0.156 ؎ 0.132 M). At those concentrations, ADA1 would be expected to be functionally dominant due to its higher affinity for adenosine. ADA1 activity in RA SF (mean ؎ SD 14.4 ؎ 8.5 IU/liter) was significantly higher than that in OA SF (3.0 ؎ 1.1 IU/liter) or RA sera (3.0 ؎ 0.6 IU/liter); moreover, ADA1 activity in RA FLS lysate was the highest among the cell lysates tested. Proinflammatory cytokines did not affect ADA1 activity or ADA mRNA expression in RA FLS.Conclusion. Elevated ADA1 activity is an intrinsic characteristic of RA FLS, which likely contributes to the pathogenesis of RA by neutralizing the antirheumatic properties of endogenous adenosine.

Presepsin and procalcitonin may be useful to identify infection in RA patients. Presepsin may better reflect infection severity than procalcitonin.

Autoimmune diseases have several etiologies. Acute Chlamydia pneumoniae (C. pneumoniae) infection may be involved in the pathogenesis of several autoimmune diseases. In this study, 82 patients with several autoimmune diseases and 70 controls were enrolled, and acute C. pneumoniae infection has been evaluated by monitoring the levels of IgM antibody. Chlamydia pneumoniae IgM positive results were observed in 29% (P < 0.05) of the patients with several autoimmune diseases and in 10% of the controls. Chlamydia pneumoniae IgM positive cases were more frequent among the patients with rheumatoid arthritis (RA; 30%, P < 0.05), systemic lupus erythematosus (SLE; 28.0%, P < 0.05), dermatomyositis/polymyositis (23%, NS), myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis (33%, NS), adult onset of Still's disease (29%, NS) and giant cell arteritis/Takayasu arteritis (50%, NS) than among the controls. This positive frequency was statistically significant in RA and SLE. These results suggest that acute C. pneumoniae infection is probably involved in the pathogenesis of autoimmune diseases.

Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2'-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.