Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin

Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin.BackgroundProstaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cyclooxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis-associated amyloidosis (HAA) by characterizing COX-2 expression in β2-microglobulin–treated human synovial cells.MethodsWe examined the effects of β2-microglobulin (β2m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction.Resultsβ2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of β2m–containing media by anti-β2m–specific antibody abrogated β2m–mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in β2m–stimulated synovial cells.ConclusionsOur results suggest that induction of COX-2 expression by β2m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy

Abnormal Liver Function in Patients with Sjogren\u27s Syndrome

We measured the liver function tests of 145 patients with Sjogren\u27s syndrome (SjS) (75 patients with primary SjS, 70 patients with secondary SjS), and characterized the SjS patients with abnormal liver function tests from several points of view : 1, the incidence of them in the primary SjS comparing with that in secondary SjS. 2, the staining pattern of anti-nuclear antibodies, and 3, the existence of antihepatitis C virus (HCV) antibody, hepatitis B surface (HBs) antigen, and antibody against human T-lymphotropic virus type I (HTLV-I). Abnormal liver function tests were detected in 38 out of 145 patients (26.2%) with SjS. Fifteen of the 38 patients (20.0%) had primary SjS while the remaining patients (32.9%) had secondary SjS. Histopathological examination identified primary biliary cirrhosis (PBC) in 2 patients, autoimmune hepatitis in 4 patients, and autoimmune cholangitis in a single patient with SjS. No significant difference in the presence of antinuclear antibody (ANA) was found between SjS patients with and without abnormal liver function tests. However, the incidence of discrete speckled pattern was significantly higher in SjS patients with abnormal liver function than in the patients with normal liver function. Two sera showing cytoplasmic pattern of ANA were also positive for anti-mitochondrial M2 antibody, allowing the diagnosis of PBC. All 11 sera exhibiting discrete speckled pattern contained significant amounts of anti-centromere antibody. Abnormal liver function tests were detected in 8 of 11 sera with these antibodies, 2 patients with PBC, 2 patients with autoimmune hepatitis, one patient with autoimmune cholangitis, one patient with chronic hepatitis B and 2 other patients with unconfirmed diagnosis. The percentages of anti-HCV antibody-positive, HBs-Agpositive and anti-HTLV-I antibody-positive in sera of patients were higher than those of blood donors from the same geographical area. However, no significant difference was seen of these percentages in sera between the patients with and without abnormal liver function. Taken together, present study indicated that SjS patients with anti-centromere antibody may have some susceptibility for acquiring autoimmune liver disease

Prediction of DAS28-ESR remission at 6 months by baseline variables in patients with rheumatoid arthritis treated with etanercept in Japanese population

We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX