血清基质金属蛋白酶3水平与早期类风湿关节炎病情评估
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摘要
目的:研究血清基质金属蛋白酶3(matrix metalloproteinase 3,MMP3)在C-反应蛋白(C-reaction protein,CRP)和/或红细胞沉降率(erythrocyte sedimentation rate,ESR)正常的早期类风湿关节炎(early rheumatoid arthritis,ERA)患者中的表达及在病情评估中的意义。方法:选择北京大学人民医院2011年至2015年确诊的早期RA患者133例,骨关节炎(osteoarthritis,OA)患者25例,健康对照组60例,其中早期RA患者根据CRP、ESR水平分为4组,CRP升高ESR升高组88例,CRP正常ESR正常组15例,CRP正常ESR升高组17例,CRP升高ESR正常组13例,回顾患者临床资料,并采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)法测定患者及健康对照血清中MMP3水平。结果:CRP正常和/或ESR正常患者血清MMP3水平[(72. 89±6. 34)μg/L]明显高于OA组MMP3[(42. 87±4. 14)μg/L](P=0. 002)和健康对照组MMP3水平[(31. 62±2. 88)μg/L](P <0. 001),其中,CRP正常ESR正常患者血清MMP3水平[(47. 04±9. 64)μg/L]高于健康对照组,差异具有统计学意义(P <0. 05),CRP升高ESR正常患者血清MMP3水平[(94. 18±9. 11)μg/L]和CRP正常ESR升高患者血清MMP3水平[(79. 42±10. 60)μg/L]均高于OA组和健康对照组,差异有统计学意义(P <0. 05)。在CRP正常和/或ESR正常的早期RA患者中,血清MMP3水平与CRP水平呈正相关(r=0. 336,P=0. 024)。CRP正常和/或ESR正常患者MMP3阳性率为44. 44%,高于CRP阳性率(28. 89%)和ESR阳性率(37. 78%),其中CRP正常ESR升高组阳性率52. 94%,CRP升高ESR正常组阳性率53. 85%。结论:血清MMP3水平的测定对于CRP和/或ESR正常的病程小于2年的早期类风湿关节炎患者具有辅助评估价值。
Objective: To investigate the expression level of serum matrix metalloproteinase 3( MMP3)in early rheumatoid arthritis( ERA) patients with normal C-reaction protein( CRP) or erythrocyte sedimentation rate( ESR),and the significance in disease assessment. Methods: In the study,133 cases of early RA patients,25 osteoarthritis( OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR,15 patients with normal CRP and normal ESR,17 patients with normal CRP but increased ESR,and 13 patients with increased CRP but normal ESR. All the clinical information of the patients was collected,and the serum MMP3 levels of both patients and healthy controls were detected by enzyme-linked immune sorbent assay( ELISA). Results: The serum MMP3 level of RA patients with normal CRP and/or normal ESR[( 72. 89 ± 6. 34) μg/L]was obviously higher than that of OA patients [( 42. 87 ± 4. 14) μg/L]( P =0. 002) and healthy controls [( 31. 62 ± 2. 88) μg/L]( P < 0. 001). The serum MMP3 levels of the patients with normal CRP and normal ESR[( 47. 04 ± 9. 64) μg/L] were higher than those of the healthy controls,and there was statistical significance between the two groups( P < 0. 05). The serum MMP3 levels of the patients with increased CRP but normal ESR [( 94. 18 ± 9. 11) μg/L]and the patients with normal CRP but increased ESR [( 79. 42 ± 10. 60) μg/L]were both higher than those of the OA patients and healthy controls,and there was obvious statistical difference( P < 0. 05). In the early RA patients with normal CRP and/or normal ESR,the serum MMP3 level was positively correlated with the CRP level( r = 0. 336,P = 0. 024). The positive rate of MMP3 in the patients with normal CRP and/or normal ESR was 44. 44%,higher than the positive rate of CRP( 28. 89%) and the positive rate of ESR( 37. 78%).In these early RA patients,the positive rate was 52. 94% in the patients with normal CRP but increased ESR and 53. 85% in the patients with increased CRP but normal ESR. Conclusion: The detection of the serum MMP3 level was significant in the assessment of early RA patients within 2-year duration who had normal CRP or ESR value.
Objective: To investigate the expression level of serum matrix metalloproteinase 3( MMP3)in early rheumatoid arthritis( ERA) patients with normal C-reaction protein( CRP) or erythrocyte sedimentation rate( ESR),and the significance in disease assessment. Methods: In the study,133 cases of early RA patients,25 osteoarthritis( OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR,15 patients with normal CRP and normal ESR,17 patients with normal CRP but increased ESR,and 13 patients with increased CRP but normal ESR. All the clinical information of the patients was collected,and the serum MMP3 levels of both patients and healthy controls were detected by enzyme-linked immune sorbent assay( ELISA). Results: The serum MMP3 level of RA patients with normal CRP and/or normal ESR[( 72. 89 ± 6. 34) μg/L]was obviously higher than that of OA patients [( 42. 87 ± 4. 14) μg/L]( P =0. 002) and healthy controls [( 31. 62 ± 2. 88) μg/L]( P < 0. 001). The serum MMP3 levels of the patients with normal CRP and normal ESR[( 47. 04 ± 9. 64) μg/L] were higher than those of the healthy controls,and there was statistical significance between the two groups( P < 0. 05). The serum MMP3 levels of the patients with increased CRP but normal ESR [( 94. 18 ± 9. 11) μg/L]and the patients with normal CRP but increased ESR [( 79. 42 ± 10. 60) μg/L]were both higher than those of the OA patients and healthy controls,and there was obvious statistical difference( P < 0. 05). In the early RA patients with normal CRP and/or normal ESR,the serum MMP3 level was positively correlated with the CRP level( r = 0. 336,P = 0. 024). The positive rate of MMP3 in the patients with normal CRP and/or normal ESR was 44. 44%,higher than the positive rate of CRP( 28. 89%) and the positive rate of ESR( 37. 78%).In these early RA patients,the positive rate was 52. 94% in the patients with normal CRP but increased ESR and 53. 85% in the patients with increased CRP but normal ESR. Conclusion: The detection of the serum MMP3 level was significant in the assessment of early RA patients within 2-year duration who had normal CRP or ESR value.
引文
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[5] Hiura K,Iwaki-Egawa S,Kawashima T,et al. The diagnostic utility of matrix metalloproteinase-3 and high-sensitivity C-reactive protein for predicting rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-negative patients with recent-onset undifferentiated arthritis[J]. Rheumatol Int,2013,33(9):2309-2314.
[6]马剑达,王晓莹,莫颖倩,等.血清基质金属蛋白酶3评价类风湿关节炎患者病情活动的价值[J].中华医学杂志,2015,95(47):3823-3828.
[7] Lee YC,Hackett J,Frits M,et al. Multibiomarker disease activity score and C-reactive protein in a cross-sectional observational study of patients with rheumatoid arthritis with and without concomitant fibromyalgia[J]. Rheumatology(Oxford),2016,55(4):640-648.
[8] Ma JD,Wei XN,Zheng DH,et al. Continuously elevated serum matrix metalloproteinase-3 for 3-6 months predict one-year radiographic progression inrheumatoid arthritis:a prospective cohort study[J]. Arthritis Res Ther,2015,14(17):289-302.
[9] Ainola MM,Mandelin JA,Liljestrom MP,et al. Pannus invasionand cartilage degradation in rheumatoid arthritis:involvement of MMP-3 and interleukin-1β[J]. Clin Exp Rheumatol,2005,23(5):644-650.
[10] Takeshita M,Kuno A,Suzuki K,et al. Alteration of matrix metalloproteinase-3O-glycan structure as a biomarker fordisease activity of rheumatoid arthritis[J]. Arthritis Res Ther,2016,18(1):112-121.
[11] Houseman M,Potter C,Marshall N,et al. Baseline serum MMP-3 levels in patients with rheumatoid arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up[J]. Arthritis Res Ther,2012,14(1):30-36.
[12] Shiozawa K,Yamane T,Murata M,et al. MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy[J]. Arthritis Res Ther,2016,18(1):55-64.
[13] Urata Y,Uesato R,Tanaka D,et al. Treating to target matrix metalloproteinase 3 normalisation together with disease activity score below 2. 6 yields better effects than each alone in rheumatoid arthritis patients:T-4 study[J]. Ann Rheum Dis,2012,71(4):534-540.
[14]孔卓,吴俊,张海文,等.血清基质金属蛋白酶3与类风湿关节炎的相关性研究[J].标记免疫分析与临床,2014,21(6):636-639.
[15]李立新,蔡蓓,廖竞宇,等.血清基质金属蛋白酶3对类风湿性关节炎患者骨关节损伤和疗效评估的价值[J].细胞与分子免疫学杂志,2013,29(9):966-969
[16]史睿,韩玲,陈慕芝,等. MMP-3、TIMP-1及HCgp-39在早期RA患者血清中的变化及意义[J].检验医学与临床,2017,14(3):325-327.
[2]葛均波,徐永健.内科学[M]. 8版.北京:人民卫生出版社,2014:808-814.
[3] Mittal R,Patel AP,Debs LH,et al. Intricate functions of matrix metalloproteinases in physiological and pathological conditions[J]. J Cell Physiol,2016,231(12):2599-2621.
[4]耿学丽,武英伟,孙常铭,等.类风湿关节炎患者基质金属蛋白酶-3的检测[J].广东医学,2016,37(4):555-557.
[5] Hiura K,Iwaki-Egawa S,Kawashima T,et al. The diagnostic utility of matrix metalloproteinase-3 and high-sensitivity C-reactive protein for predicting rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-negative patients with recent-onset undifferentiated arthritis[J]. Rheumatol Int,2013,33(9):2309-2314.
[6]马剑达,王晓莹,莫颖倩,等.血清基质金属蛋白酶3评价类风湿关节炎患者病情活动的价值[J].中华医学杂志,2015,95(47):3823-3828.
[7] Lee YC,Hackett J,Frits M,et al. Multibiomarker disease activity score and C-reactive protein in a cross-sectional observational study of patients with rheumatoid arthritis with and without concomitant fibromyalgia[J]. Rheumatology(Oxford),2016,55(4):640-648.
[8] Ma JD,Wei XN,Zheng DH,et al. Continuously elevated serum matrix metalloproteinase-3 for 3-6 months predict one-year radiographic progression inrheumatoid arthritis:a prospective cohort study[J]. Arthritis Res Ther,2015,14(17):289-302.
[9] Ainola MM,Mandelin JA,Liljestrom MP,et al. Pannus invasionand cartilage degradation in rheumatoid arthritis:involvement of MMP-3 and interleukin-1β[J]. Clin Exp Rheumatol,2005,23(5):644-650.
[10] Takeshita M,Kuno A,Suzuki K,et al. Alteration of matrix metalloproteinase-3O-glycan structure as a biomarker fordisease activity of rheumatoid arthritis[J]. Arthritis Res Ther,2016,18(1):112-121.
[11] Houseman M,Potter C,Marshall N,et al. Baseline serum MMP-3 levels in patients with rheumatoid arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up[J]. Arthritis Res Ther,2012,14(1):30-36.
[12] Shiozawa K,Yamane T,Murata M,et al. MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy[J]. Arthritis Res Ther,2016,18(1):55-64.
[13] Urata Y,Uesato R,Tanaka D,et al. Treating to target matrix metalloproteinase 3 normalisation together with disease activity score below 2. 6 yields better effects than each alone in rheumatoid arthritis patients:T-4 study[J]. Ann Rheum Dis,2012,71(4):534-540.
[14]孔卓,吴俊,张海文,等.血清基质金属蛋白酶3与类风湿关节炎的相关性研究[J].标记免疫分析与临床,2014,21(6):636-639.
[15]李立新,蔡蓓,廖竞宇,等.血清基质金属蛋白酶3对类风湿性关节炎患者骨关节损伤和疗效评估的价值[J].细胞与分子免疫学杂志,2013,29(9):966-969
[16]史睿,韩玲,陈慕芝,等. MMP-3、TIMP-1及HCgp-39在早期RA患者血清中的变化及意义[J].检验医学与临床,2017,14(3):325-327.