Transforming growth factor beta 1 gene polymorphism in Japanese patients with systemic lupus erythematosus.

To determine the role of transforming growth factor beta 1 (TGFbeta1) gene polymorphisms in the pathogenesis of systemic lupus erythematosus (SLE), we investigated the polymorphisms of T869C of the TGFbeta1 gene in 196 patients with SLE and 106 healthy controls by analyzing polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies of T869C of the TGFbeta1 gene did not differ between SLE and healthy controls. However, compared to the TC and CC genotypes, the TT genotype was associated with anti-SS-A/Ro antibody production (p=0.029) and a higher incidence of aseptic necrosis (p=0.0097); the CC genotype had a higher frequency of anti-RNP antibody production compared to the patients with the TC and TT genotypes (p=0.023). These results suggest that T869C polymorphism of the TGFbeta1 gene is involved in the development of autoantibodies and the occurrence of aseptic necrosis in patients with SLE. Thus, TGFbeta1 polymorphism might be one of the genetic factors that explain the heterogeneity seen with SLE.

Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis.

There is no doubt that oxidative stress occurs in patients with rheumatoid arthritis (RA) and play an important role in both inflammation and destruction of RA joints. Thioredoxin (TRX) is a ubiquitous redox-active protein and is known to be induced in several cells against oxidative stress and to be secreted extracellularly. To clarify whether plasma thioredoxin levels could be a marker for oxidative stress in patients with RA, we measured plasma TRX levels in patients with RA using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) and investigated its relationship to TRX concentrations in the inflammatory joints. We have found that the plasma TRX levels of RA patients were significantly higher than those of normal subjects (86.8 +/-54.1 ng/ml versus 38.6 +/-18.5 ng/ml, P<0.0001). The plasma levels were correlated with the disease activity of RA and also with serum C-reactive protein (CRP) values (P<0.01). The concentration of TRX in synovial fluid (SF) from RA was 353.3 +/- 220.1 ng/ml (mean +/- S.D.) which was significantly higher than that in SF from osteoarthritis patients (70.6 +/- 31.0 ng/ml, P<0.0001). The SF TRX concentration was significantly correlated with the number of leukocytes infiltrating in SF and with the serum CRP levels. The serum TRX levels were significantly positively correlated with the SF TRX concentrations in RA patients (P<0.05). By the histological examination for synovial tissue of RA patients, TRX was shown to be present on the surface of synovial lining layer as well as in the leukocytes.Moreover, urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage by endogenously generated oxygen radicals, was significantly higher in RA patients than in healthy subjects (11.55 +/- 4.71 versus 7.76 +/- 2.26 ng/mg creatinine, P<0.0001). Plasma TRX levels were significantly correlated with urinary excretion of 8-OHdG (P<0.005). We concluded that plasma TRX level is a new biomarker for the disease activity of RA and may reflect higher levels of oxidative stress in RA patients.