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Objective To explore the effect of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein injection (rhTNFR:FC) on the expression of cartilage oligomeric matrix protein (COMP) in the synovial fluid and peripheral blood of juvenile idiopathic arthritis (JIA); and to explore the clinical significance of COMP for JIA and the relationship between rhTNFR:FC and COMP in JIA.Methods Thirty-five patients with JIA (JIA group),30 patients with traumatic arthritis (trauma group) and 30 patients with indirect inguinal hernia hernioplasty (normal group) were included.Peripheral blood from all enrolled patients and synovial fluid from 15 JIA and 10 trauma arthritis were obtained for COMP detection before the treatment.Fifteen JIA (group A) patients were treated with combined rhTNFR:FC,diseasemodifying antirheumatic drugs (DMARDs) and non-steroid anti-inflammatory drugs (NSAIDs),20 JIA (group B) were treated with combined DMARDs and NSAIDs.After three to six months' treatment and when the disease were in remission,peripheral blood from group A and B were drawn for COMP detection.In group A,the synovial fluid from 5 patients were obtained for COMP detection after treatment.At the same time,such as tender joint count (TJC),swollen joint count (SJC),time for morning stiffness,blood routine,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and other parameters before and after treatment were measured.The level of COMP was tested by double antibody sandwich enzyme-linked immunosorbent assay.The measurement data were tested for variance and independent sample t-test; and the enumeration data were tested by chi-squared or Fisher's exact test.Pearson's correlation analysis was adopted to analyze the association among the variables.Results ① The blood COMP level before treatment was (0.77±0.29) ng/ml in the JIA group,(1.00±0.28) ng/ml in the traumatic arthritis group,and (1.33±0.37) ng/ml in the normal control group.The level in the former two groups was obviously lower than that in the normal control group.The variation was statistically significant (F=25.345,P＜0.05).The comparison between any two groups was statistically significant (P＜0.05).② The COMP level in the synovial fluid before treatment were (14.8±1.6) ng/ml in the JIA group,(15.1±1.0) ng/ml in the traumatic arthritis group.The variation was not stati-stically significant (t=0.523,P=0.606).③ The serum COMP level of the systemic JIA group was obviously lower than that of the oligoarticular JIA patients,and patients with enthesitis-related arthritis and polyarticular JIA (0.26± 0.03 vs.0.87±0.17,0.89±0.22 and 0.70±0.35 ng/ml,respectively; F=9.244,P＜0.05).④ The serum COMP level of JIA at the acute phase was negatively correlated with white blood cells count (WBC),CRP and ESR (r=-0.556,-0.582 and-0.684,respectively; P all＜0.05).By contrast,no correlation was detected between the serum COMP level and joint tenderness index,joint swelling index,morning stiffness duration,hemoglobin level and platelet count(r=0.06,-0.206,-0.107,0.15 and-0.185,respectively; P all ＞0.05).⑤ The serum COMP level was obviously lower in the JIA with joint destruction than that without joint destruction (0.52±0.22 vs.0.92±0.22 ng/ml; t=5.207,P＜0.05).⑥After treatment,the blood COMP level in group A was (1.33±0.21) ng/ml and (0.96±0.22) ng/ml in group B,which was obviously higher than that in the JIA group before treatment (0.77±0.29) ng/ml.In addition,the level in group A was higher than that in group B.The variation was statistically significant (F=24.681,P＜0.05).⑦ After treatment,the COMP level in the synovial fluid (18.4± 1.1) ng/ml (n=5) was higher than that before the treatment was (14.8± 1.6) ng/ml (n =15).The variation was of statistical significant (t=4.565,P＜0.05).Conclusion The COMP level in blood and synovial fluid declines before treatment and increases after treatment.The increase is more obvious after combined with rhTNFR:FC treatment.The serum COMP level is remarkably decreased in JIA at the acute phase,systemic JIA,and the JIA with destruction of joint,and showes a negative correlation with WBC,CRP and ESR.Serum COMP may be a useful marker of active disease,destruction of joint and growth inhibition for patients with JIA.rhTNFR:FC treatment for JIA can facilitate the recovery of COMP.
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Objective To analyze the outcome of children with juvenile idiopathic arthritis (JIA) treated with recombinant human tumor necrosis factor receptor antibody fusion protein (rhTNFR:Fc) for 2 years,and to evaluate the long-term efficacy and safety as well as the related factors that affect the curative effect of rhTNFR:Fc.Methods Fifty-seven JIA patients treated with rhTNFR:Fc were followed up for 2 years.Clinical data were registered including age of onset,disease duration before rhTNFR:Fc treatment,disease activity assessment,medication before treatment,dosage regimen of infection or adverse reactions.Pearson Chi-Square statistical test and logistic regression model of binomial classification were used for statistical analysis.Results ①Twenty-two JIA cases completed 2-year therapy.Some were in the process of dosage tapering.Eight cases reached ACR Pedi 50,14 cases reached ACR Pedi 70.All of them were included in the clinical effectiveness analysis.Thirty-five cases withdrawal in 2 years because of disease remission or treatment failure or side effects or infection.Seven who withdrew and then maintained with DMARDs under the supervision of doctors were evaluated by assessment of ACR Pedi 70.They were stable at the end of 2 years,and were included for the clinical effectiveness analysis group.Nineteen cases were withdrew by the doctor because they failed to reach ACR Pedi 30 within 3 months.They were included in the treatment failure analysis.Seven cases were lost during the follow up.② The remission rate (ACR Pedi 50,70) of SO-J1A in 2 years was 33％.Oligoarthritis rate was 60％,while that of polyarthritis rate was 79％.The statistical analysis showed that different categories and RF level were significantly different in effectiveness and treatment failure (x2=31.6,P＜0.05; x2=5.488,P＜0.05).There was no significant difference in age,sex,duration before treatment,AKA,CCP,ANA between the two groups (P＞0.05).③ Logistic regression analysis showed that different categories of JIA and RF levels were correlated with therapy,P＜0.05.The relative risk (OR) value of different categories of JIA was 2.983 (P＜0.05).Negative RF might be the predictive factor for treatment response (OR =0.029,P＜0.05).④ Eight cases (2％) had recurrence and other adverse reations during treatment,the majority (7 cases) was SO-JIA.Conclusions ① The long-term therapeutic effect and safety for oligoarthritis and Polyarthritis by rhTNFR:Fc are better than SO-JIA.② Negative RF maybe the factor associated with favourable rhTNFR:Fc efficacy.③ The long-term safety of rhTNFR:Fc for SO-JIA is good.Physicians should be cautious to infection and other adverse reactions.
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Objective To explore the effects of tumor necrosis factor-α (TNF-α) on ventricular arrhythmias resulted from acute myocardial infarction (AMI) in rats. Method Two hundred and forty male Wistar rats were randomized (random number) into sham operation group, AMI group and recombinant human tumor necrosis factor receptor (rhTNFR) fusion protein (Fc) group. Acute anterior wall myocardial infarction was produced in rats of AMI group with ligating the left anterior descending coronary artery (LAD) , and the rats were just operated without ligation of LAD in sham group. The rats of Fc group were treated with rhTNFR-Fc (10 mg/kg), a TNF-α antagonist, 24 hours before LAD ligation. The original ECG was recorded 10 min before ligation and the ECGs of ventricular arrhythmias occurred spontaneously or induced by programmed electrical stimulation were recorded 10 min, 20 min, 30 min, 60 min, 3 h, 6 h and 12 hours after ligation. The protein levels and mRNA expressions of TNF-α in rats in different groups were detected with histochemistry and real-time fluorescent quantitative PCR. Results The expressions of TNF-α mRNA and levels of TNF-α protein markedly increased 10 min after infarction, reached the climax 20-30 min later, and then gradually returned to the original level in AMI group and Fc group. The time-windows of spontaneous and induced ventricular arrhythmias were consistent with the time-window of expressions of TNF-α mRNA and levels of TNF-α protein. Compared with AMI group, there were lower levels of TNF-α protein and lower incidence of ventricular arrhythmias in Fc group ( P < 0.05) , but there was no significant difference in TNF-α mRNA between two groups. There was no obvious change in TNF-α in rats of sham operation group. Conclusions The expressions of TNF-α mRNA and levels of TNF-α protein induced by AMI could contribute the initiation of ventricular arrhythmias.
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Objective To investigate the efficacy and tolerability of a recombinant human tumor necrosis factor:Fc fusion protein (rhTNFR:Fc,with a trade name of Yisaipu) in the treatment of moderate to severe psoriasis vulgaris.Methods A multicentre,randomized,double blind,and parallel-controlled trial was performed.One hundred and forty-four patients with moderate to severe psoriasis vulgaris from four centres were randomly assigned and treated with either once-weekly subcutaneous injection of rhTNFR:Fc (50 mg) or oral methotrexate (MTX)(7.5 mg) for 12 weeks.Patients were followed up at 2,4,8,12 weeks after the treatment.Results One hundred and twenty-four patients finished the 12-week course of treat- ment.At 12 weeks after the treatment,a 50%,75%,90% improvement in psoriasis area and severity index (PASI) was achieved by 86.11%,76.39%,52.78% respectively of rhTNFR:Fc-treated patients,and by 63.89%,44.44%,22.22% respectively in MTX-treated patients,and all the three improvement rates were of significant difference between the two groups of patients (all P0.05).Conclusion Compared with MTX,rhTNFR:Fc acts more quickly with a higher cure rate and less toxic reactions in the treatment of psoriasis vulgaris.
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AIM:To investigate the mechanisms and protective effects of recombinant human tumor necrosis factor receptor :Fc fusion protein(rhTNFR:Fc)on the acute lung injury induced by lipopo1ysaccharide(LPS)in rats.METHODS:The rat model of acute lung injury was established with LPS and the rats were randomly divided into four groups:control group,rhTNFR:Fc group,LPS group and rhTNFR:Fc+LPS group.After administration,the rats' death was recorded,the pulmonary wet/dry weight ratios were determined,the changes of lung histopathology were observed by HE dyeing,the levels of TNF-? and the bioactivity in serum were detected.RESULTS:Compared with control group the rats' mortality rate and pulmonary wet/dry weight ratio were significantly higher in the LPS group(P