Evaluation Of Serum MMP-3 And US7 Score In Patients With Rheumatoid Arthritis

Rheumatoid arthritis is a synovial inflammation which is the main pathological manifestation of chronic,systemic autoimmune disease.Early assessment and treatment of patients with joint injury is the key point in clinical work.Clinically,evaluation RA disease activity indicators such as DAS28,SDAI,CDAI etc.,require complex formula and joint swelling,tenderness,erythrocyte sedimentation rate,C~reactive protein and VAS score multiple indicators and cannot directly reflect the RA of the cartilage and bone destruction.So it is urgent to find a simple and accurate assessment method.Matrix metalloproteinase 3(MMP-3)is mainly involved in tissue matrix and collagen degradation,and is closely related to joint damage.It was found that the content of MMP-3 in the synovial membrane of RA was significantly increased,and the MMP-3 protein and gene were in the over expression state,which suggested that MMP-3 was one of the indicators for the degradation of cartilage.Ultrasonic examination has become an important diagnostic technique for RA because of its advantages such as non~invasive,no radiation,economical portability and real~time dynamic monitoring.Gray scale ultrasound(GS)can be real~time dynamic observation of effusion,synovial and periarticular soft tissues,tendons,cartilage and bone erosion.Energy Doppler ultrasound(PD)studies show that it is related to the activity of the disease and is more sensitive than clinical indicators.MMP-3 is able to prompt RA in patients with cartilage degradation of serum indicators,and ultrasound is able to directly reflect the image of RA patients,and in clinical practice is simple and practical.So this study firstly try to combine the two together to jointly evaluate the activity of RA patients and the efficacy in the treatment process,in order to find a more accurate and convenient way to assess the condition of RA.Part I: Evaluation of serum MMP-3 in patients with rheumatoid arthritisObjective: By comparing the levels of serum MMP-3 in RA patients with different disease activity,the feasibility of serum MMP-3 for RA disease activity evaluation was studied.Methods: Immune turbidimetric method determination of 151 cases in different active RA serum MMP-3 levels in patients with,and clinical data were collected simultaneously,and determination of erythrocyte sedimentation rate(ESR)and anti CCP antibody,HAQ,DAS28 and other indicators,the correlation analysis between each index.Results: Compared with the serum MMP-3 level in healthy controls 35.20(25.90~48.90)and RA patients with remission disease activity 33.40(22.60~678.42),the MMP-3 levels in RA patients with moderate(105.10(61.70~172.71))and high(363.11(161.52~475.92)disease activity increased dramatically.The level of MMP-3 in RA patients was positively correlated with DAS28,HAQ,US7,and no correlation with anti CCP antibody levels.Conclusions: MMP-3 is an effective and simple index in evaluating RA disease activity.Part II: Evaluation of US7 score of joint ultrasound in patients with rheumatoid arthritisObjective: By comparing the level of US7 in rheumatoid arthritis(RA)patients with different disease activity,and to explore the clinical evaluation of US7 score in RA.Methods: Color Doppler ultrasound determination of 151 cases in different active RA patients with US7 score and to analyze its correlation with the erythrocyte sedimentation rate(ESR)and anti CCP antibody,HAQ,DAS28 and other indicators;and the analysis of the US7 score in different area of the joint score weight.Results: 1)The US7 score of RA patients with severe active was significantly different from that in RA patients with stable and regular,mild and moderate active(7.8 VS0.8 P<0.0001,7.8 VS 2.2,P=0.0151;7.8 VS 3.2,P=0.0398).Ultrasonic US7 with DAS28(r=0.487,P<0.001),HAQ(r=0.434,P<0.001),ESR(r=0.384,P<0.001)were positively correlated,no correlation with anti CCP antibody(r=-0.174,P=0.200).2)The US7 score found gray scale synovitis(GS)of the highest proportion of synovitis of GS(63.1%),synovitis blood flow signal(PD)(18.3%),tenosynovitis GS(7.4%),tenosynovitis PD(4.3%),bone destruction(6.9%).The highest proportion of the joint area is the dorsal wrist joint(16.3%),and the second is the palm side MCP II(9.8%).Conclusions: The ultrasound US7 score can effectively reflect the disease activity of RA patients,especially for RA patients with severe active have better evaluation value.In the US7 score,proportion of synovitis was significantly higher than that of tenosynovitis and bone destruction,the most easily involving the joint is dorsal wrist and palmar side of the MCPII.We need to pay more attention to the changes in the two joint area in clinical.Part III: Evaluation of MMP-3 and US7 in rheumatoid arthritisObjective: By comparing the levels of serum MMP-3 and US7 score in RA patients,the correlation between serum MMP-3 and ultrasound was studied,and the feasibility of using both of them together for RA disease assessment was observed.Methods: Immune turbidity and color Doppler ultrasound determination of 151 cases of RA patients in different activities of serum MMP-3 levels and US7 score,erythrocyte sedimentation rate(ESR)were compared,anti CCP antibody,HAQ,DAS28 and index analysis,the correlation among the indexes.Using ROC curve to describe MMP-3,US7 and MMP-3+US7 to distinguish the degree of disease activity.Results: 1)The level of MMP-3 in patients with RA was significantly positively correlated with US7(r=0.566 P<0.001).2)US7 score as a reference standard,MMP-3 value to do ROC curve(Area under the curve 0.8538,P< 0.0001).The MMP-3 cutoff value corresponding to 70.5ng/ml.MMP-3 and MMP-3+US7(1.463 ± 0.3085 VS 6.457 ± 0.5295 P< 0.0001);DAS28(3.692 ± 0.1424 VS 4.989 ± 0.1436 P< 0.0001)has significant difference.3)Using DAS28 as a reference standard,the ROC curve was used to describe the MMP-3?US7and MMP-3+US7 degree of disease activity.The results showed that the combined application of MMP-3 and US7 in disease activity judgment,compared with the use of MMP-3 alone(Area under the curve 0.8632 vs 0.8543,P>0.05),the difference was not statistically significant.The difference was statistically significant compared with US7 alone(Area under the curve 0.8632 vs 0.7643,P<0.01).Conclusions: There was significant correlation between MMP-3 and US7,DAS28 and US7 in MMP-3 positive group and MMP-3 negative group had significant difference.The activity of RA and the change of joint inflammation in patients with MMP-3 were suggested.MMP-3>70.5ng/ml,a high degree of suspicion of inflammation of the joints.The combined use of MMP-3 and US7 with respect to MMP-3 did not improve the efficacy of the evaluation of activity in patients with RA.Part IV: Evaluation of baseline MMP-3 levels for the prognosis of RA patientsObjective: The US7 score was used as an imaging index to observe whether the MMP-3 level of baseline can reflect the progression of RA patients' joint changes.Methods:MMP-3 and US7 scores of 30 patients with active RA were detected before and after 12 weeks,evaluation of the baseline period of MMP-3 can predict the US7 score after 12 week.Results: MMP-3(222.34±154.23 VS 167.82±160.41,p<0.001)and US7(7.26±5.76 VS 5.21±6.32 p<0.001)of 30 patients with active RA were significantly increased between the before and after treatment.Baseline MMP-3 levels were correlated with US7 score at 12 weeks(r=0.503,p=0.033),and were also found to have significant correlation with?US7 and?ESR(r=0.603,p=0.011;r=0.549,p=0.018).Baseline levels of MMP-3 and other serological indexes such as ESR,CRP,HAQ,anti CCP,joint swelling,joint tenderness and difference had no significant.Conclusions: Baseline MMP-3 levels were good predictors of the development of RA patients.PART V: Efficacy evaluation of MMP-3 and ultrasound US7 score in the treatment of patients with CimziaObjective: To observe the effect of MMP-3 and US7 in the treatment of RA.Methods:MMP-3 and US7 scores were observed in 22 patients with active RA who were treated with Cimzia for 24 weeks,and 17 patients with active RA who were treated with Cimzia for 48 weeks.Results:MMP-3 and US7(94.11±74.96 VS 214.8±160.4,3.1±3.09 VS 8.7±8.61 P<0.01)were significantly decreased compared with the baseline period in 22 patients with RA who were treated with Cimzia for 2 weeks.2)There is a significant difference in ?MMP-3(124.365±107.828 VS 69.139±33.066;127.828±220.685 VS 76.244±49.253 P<0.01)between 22 ACR50?ACR70 positive and negative patients who were treated for 24 weeks.After 12 weeks of treatment,there was significant difference in US7 score(9.154±8.061 VS 1.143±1.215;13.25±7.704 VS 1.75±1.658 P<0.01)between ACR50 and ACR70 positive and negative patients.The results were the same in 24 weeks(9.692±7.836 VS 0.857±1.676;11.7±7.775 VS 1.5±2.224 P<0.01).3)In 17 patients after 1 years,both MMP-3 and US7 showed a significant decrease(P<0.01)between W0 and W12,W24,W36,W48.Conclusions:MMP-3 and US7 scores were able to respond quickly to the remission of the disease,and the decrease in the MMP-3 and US7 scores strongly suggests the efficacy of RA on the biological agents.