Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoarthritis

The cartilage oligometrix matrix protein (COMP) is a noncollagenous protein, a glycoprotein, the function of which is to bind to type II collagen fibres and stabilise the collagen fibre network in the articular cartilage. In the serum of the normal population the COMP level is 5 g/ml. An increased level of COMP in the synovial fluid was described in the early stage of rheumatoid arthritis (RA), whereas in advanced stages of RA, the level of COMP decreased. In this study we assessed the serum COMP level in patients with RA and knee osteoarthritis (OA) and found a correlation between the serum COMP level and other markers as well as bone mass density (BMD) changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA patients and 30 OA patients who constituted the control group. The serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in RA patients was 10.4±3.6 U/l. There was a correlation between the serum COMP level and the age of RA patients (p<0.005) and disease activity score (DAS) value (p<0.01). According to correlation coefficients, the serum COMP level was independent of stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration and titre of the Waaler–Rose test. The influence of rheumatoid nodule presence on the serum COMP level was shown (p<0.05). In RA patients with erythrocyte sedimentation rate (ESR) values below 20 mm/h compared with patients with ESR values over 60 mm/h, the serum COMP level was observed to be significantly lower (p<0.05). The average value of COMP in OA patients was 10.4±2.7 U/l. No correlation was found between the serum COMP level and patients age and disease duration. There was a correlation between the serum COMP level and Western Ontario and McMaster Universities (WOMAC) index pain scale for the lower limbs (p<0.005) and T-score value of densitometry examinations (p<0.036) in OA patients. No statistical differences were found between the average serum COMP level in RA and OA patients.     

血清软骨寡聚基质蛋白检测在关节炎患者中的意义研究

目的 探讨血清软骨寡聚基质蛋白(COMP)在各类关节炎患者中的差别及对类风湿关节炎(RA)软骨破坏放射学改变的早期预测价值.方法 采用酶联免疫吸附试验(ELISA)方法测定并对比分析154例各类关节炎患者血清COMP水平的差异,RA患者各项临床指标及2年后关节放射学改良SHARP(vdH-Sharp)指数评分与COMP行相关性分析.结果 与仅有滑膜损害的其他关节炎患者及正常人群比较,RA患者血清COMP显著升高(P＜0.05).骨关节炎(OA)、银屑病关节炎(PSA)患者与正常人群比较血清COMP亦有差异,而与其他滑膜关节炎患者比较差异不大.RA、OA、PSA患者间血清COMP值比较差异无统计学意义.RA患者2年随访发现COMP与患者关节X线的改良SHARP评分前后差值呈正相关(P＜0.01,r=0.848).但与初诊时的抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)、关节功能、改良SHARP评分均无相关性,与初诊时的红细胞沉降率(ESR)、C反应蛋白(CRP)、晨僵时间、关节肿胀、压痛指数相关(P＜0.05).结论 COMP在各类软骨受侵犯关节炎尤其是RA患者血清中异常增高,提示其可为RA软骨病变早期诊断及判断软骨病变进展、预后和治疗效果的一项理想指标.     

Cartilage oligomeric matrix protein in serum and synovial fluid of rheumatoid arthritis: potential use as a marker for joint cartilage damage

This study examined the serum and synovial fluid concentrations of cartilage oligomeric matrix protein (COMP) in relation to the evolution of joint cartilage damage and the requirement for surgery in 125 patients with rheumatoid arthritis (RA). We compared the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and matrix metalloproteinase-3 (MMP-3) levels with COMP levels determined by specific enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups: (1) patients with least erosive disease (LES); (2) patients with more erosive disease (MES); and (3) patients with mutilating disease (MUD). In addition, synovial fluid samples were collected from patients undergoing arthroscopic synovectomy of the knee joint (ASS) and total knee arthroplasty (TKA). Serum COMP levels correlated with the ESR (P < 0.0001, r = 0.374, n = 125) and the CRP level (P = 0.0014, r = 0.281, n = 125). COMP levels did not correlate with the MMP-3 level (P = 0.182, r = 0.114, n = 125). The COMP levels of the LES group were significantly lower than those of the MES or MUD groups. Lastly, synovial fluid COMP levels in the TKA group were higher than in the ASS group. Therefore, these findings suggest that serum and synovial fluid COMP levels in patients with RA may reflect cartilage destruction and are correlated with the ESR and the CRP level, which are indicators of the acute-phase response.     

Cartilage oligomeric matrix protein in serum and synovial fluid of rheumatoid arthritis: potential use as a marker for joint cartilage damage

Abstract

This study examined the serum and synovial fluid concentrations of cartilage oligomeric matrix protein (COMP) in relation to the evolution of joint cartilage damage and the requirement for surgery in 125 patients with rheumatoid arthritis (RA). We compared the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and matrix metalloproteinase-3 (MMP-3) levels with COMP levels determined by specific enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups: (1) patients with least erosive disease (LES); (2) patients with more erosive disease (MES); and (3) patients with mutilating disease (MUD). In addition, synovial fluid samples were collected from patients undergoing arthroscopic synovectomy of the knee joint (ASS) and total knee arthroplasty (TKA). Serum COMP levels correlated with the ESR (P < 0.0001, r = 0.374, n = 125) and the CRP level (P = 0.0014, r = 0.281, n = 125). COMP levels did not correlate with the MMP-3 level (P = 0.182, r = 0.114, n = 125). The COMP levels of the LES group were significantly lower than those of the MES or MUD groups. Lastly, synovial fluid COMP levels in the TKA group were higher than in the ASS group. Therefore, these findings suggest that serum and synovial fluid COMP levels in patients with RA may reflect cartilage destruction and are correlated with the ESR and the CRP level, which are indicators of the acute-phase response.     

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients

Background Coronary artery calcification (CAC) is common in end-stage renal disease (ESRD) patients,and the extent of CAC is closely related to cardiovascular o...     

Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab

In this study, we determined serum cartilage oligomeric matrix protein (COMP) levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the active and the remission phases to investigate how the growth cartilage turnover changed under tocilizumab treatment. Specimens were collected from 201 healthy children under 16 years of age with no growth impairment, and paired sera were collected from 11 sJIA patients treated with tocilizumab. Disease activity was assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and ferritin, and the COMP concentration was determined by sandwich enzyme-linked immunosorbent assay. Serum COMP concentrations were found independent of age, and the mean value in healthy children was 17.74 ± 5.6 U/L. The mean serum COMP in sJIA patients during the active phase was 10.75 ± 3.9 U/L, lower than that of healthy children. The mean serum COMP in the remission phase (14.89 ± 3.9 U/L) was significantly higher than that in the active period (P < 0.05). These results suggested that in sJIA patients, a reduced serum COMP concentration is a useful marker of active disease and growth impairment, and that the growth cartilage turnover suppressed during the active phase is improved in the remission phase under tocilizumab treatment.     

软骨寡聚基质蛋白对骨关节炎软骨破坏早期诊断价值的研究

目的 探讨软骨寡聚基质蛋白(COMP)对骨关节炎软骨破坏早期诊断价值.方法 兔右后膝伸直位石膏管型固定法制作骨关节炎模型;形态学方法观察造模不同时期关节病理切片;免疫组织化学方法检测软骨内COMP水平;酶联免疫吸附试验(ELISA)方法检测血清COMP水平.应用t检验,Pearson相关性分析.结果 ①伸直位石膏管型制动2周,模型关节呈现早期骨关节炎改变,制动6周呈现典型的中晚期骨关节炎特征;②造模前、模型2周、模型6周血清COMP含量分别是[(3.35±0.20)、(3.64±0.18)、(3.96±0.44)μg/L,P均＜0.05];③未造模、模型2周、模型6周关节软骨内COMP表达强度分别是[(2.7±1.8)%,(5.7±0.7)%,(7.6±0.7)%,P均＜0.05];④模型2周血清COMP水平与模型2周组、模型6周组OA病理评分存在线性相关关系(r均＞0.770,P均＜0.05).结论 骨关节炎血清COMP检测对早期诊断骨关节炎软骨破坏具有重要的意义.

Abstract：

Objective To study the diagnostic value of cartilage oligomeric matrix protein for early cartilage destruction in osteoarthritis and assess its value in the prediction of the disease progression.Methods The osteoarthritis animal models were developed by immobilizing the right knees of 18 rabbits in full extension position using plaster East.Knee joint pathological changes at week 2 and 6 were examined for pathological severity evaluation of osteoarthritis.ELISA sandwich method was used to measure the levels of cartilage oligomeric matrix protein(COMP) in serum before and after modeling(at week 2 and 6 respectively) and immunohistolgy method was used to examine the levels of COMP in knee articular cartilage of osteoarthritis animal models.Correlation analysis was performed to demonstrate the relationship between the levels of COMP in the serum and the pathological severity of osteoarthritis.Pearson's test and t-test were used for correlation analysis.Results ①) Osteoarthritis animal models could be successfully developed by immobilizing the right knees of rabbits in full extension position using plaster east for 2 weeks.Early histopathological changes in the articular cartilage could be observed,At week 6,the typical histopathological characteristics could be seen.②With the extension of modeling time,serum COMP levels persistently increased.The serum COMP levels before modeling,at modeling week 2,week 6 were (3.35±0.20),(3.64±0.18),(3.96±0.44) μg/L respectively,the difference was significant (P＜0.05).③ The level of COMP in the articular cartilage of non-osteoarthritis animal models,models at week 2,week 6 were (2.7±1.8 )％ ,(5.7±0.7)％,(7.6±0.7)％ respectively (P＜0.05 for all).④ The level of COMP in the serum was linearily correlated with the pathological severity of osteoarthritis(r＞0.770 for all,and P＜0.05 for all).Conclusion Levels of COMP in the serum can help to make early diagnosis of osteoarthritis,and elevated COMP level can predict the progression of osteoarthritis.     

骨关节炎兔血清中软骨寡聚基质蛋白和基质金属蛋白酶-3水平

目的 探讨血清软骨寡聚基质蛋白(COMP)与基质金属蛋白酶(MMP)-3检测应用于临床评估骨关节炎(OA)软骨病理改变的可能性.方法 伸直位石膏管型制动16只兔右后膝关节制作OA模型.以造模时间不同分为造模2周、造模6周,左后膝关节未造模故为对照组.X线影像学与病理观察模型关节的变化;评估关节软骨降解程度(OA积分);ELISA检测兔血清COMP、MMP-3水平;分析血清COMP、MMP-3水平与OA积分间的相关性.结果 (1)造模2周影像学变化较造模前不明显;造模6周兔胫骨平台边缘不光滑,关节间隙变窄,表面有毛刺样增生,胫骨平台及股骨内髁外侧可见唇样增生.(2)OA关节病变的形态学观察:造模2周兔关节软骨表面粗糙,表层裂隙;软骨细胞弥漫增多,排列紊乱;OA积分为(4.000±2.204)分.造模6周兔关节软骨表层可见较多裂隙延伸向下深达辐射层;裂隙周围可见脱水固缩坏死的软骨细胞且排列紊乱,部分成簇增生,各层结构不易分辨,有血管翳通过;OA积分为(10.620±1.408)分,与造模2周比,P=0.000.(3)造模2周兔血清COMP[(3.64±0.18)μg/L]、MMP-3[(1.99±0.81)μg/L]水平高于造模前[COMP(3.35±0.20)μg/L,MMP-3(1.61±0.71)μg/L];造模6周兔血清COMP[(3.96±0.44)μg/L]、MMP-3[(3.44±0.91)μg/L]水平高于造模前和造模2周,差异有统计学意义(P值均＜0.05).血清COMP、MMP-3水平与OA积分呈线性相关关系(r值均＞0.710,P值均小于0.05).结论 OA血清中COMP和MMP-3水平对评估OA软骨降解程度具有重要意义.

Abstract：

Objectiye To study the levels of cartilage oligomeric matrixprotein (COMP) and matrix metalloproteinase-3 (MMP-3) in the serum fluid of osteoarthritic rabbit models and their relationships with the severity of pathological changes, so as to investigate their correlation with osteoarthritis(OA). Methods The osteoarthritic animal models were get from immobilizing the right knees of 18 rabbits in full extension using plaster cast. Knee joint pathological changes of 2,6 weeks were examined for pathological severity of OA; ELISA sandwich method was used to measure the levels of COMP and MMP-3 in serum before and after modeling( at 2, 6 weeks respectively); X ray of model keens was also obtained in different period.Correlation analysis was performed to demonstrate the relationship between the levels of COMP, MMP-3 in the serum and the pathological severity of OA. Results ( 1 ) Morphological observations: immobilizing the right knees of rabbits in full extension using plaster cast was a reliable methed for osteoarthritic animal models and the typical histopathologic character was seen; the severity of osteoarthritisgradually increased with time extended. (2) The levels of COMP[(3.64 ±0. 18)μg/L], MMP-3 [(1.99 ±0. 81 ) μg/L]in the serum of 2 weeks osteoarthritic animal models were higher than those before immobilizing with plaster cast [COMP(3.35 ±0. 20) μg/L,MMP-3( 1.61 ±0. 71 ) μg/L]. The levels of COMP[(3.96 ±0. 44) μg/L],MMP-3[(3.44 ±0. 91) μg/L] of 6 weeks were much higher,with a significant difference(P ＜0.05). The levels of COMP, MMP-3 in serum had a linear correlation with the pathological severity of OA (r ＞0. 710,and P ＜ 0. 05 ). Conclusion The levels of COMP and MMP-3 in serum can help to predict and evaluate the progression of OA.     

Persistent elevation of fibrosis biomarker cartilage oligomeric matrix protein following hepatitis C virus eradication

Serum levels of cartilage oligomeric matrix protein (COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has also been associated with hepatocellular carcinoma. We present a prospective analysis of this biomarker in 38 patients with chronic hepatitis C who were subject to eradication therapy with direct acting antivirals. We confirm previous studies associating COMP elevation with liver cirrhosis. We also show how viral levels are correlated with COMP at baseline. In our prospective analysis, we report that successful eradication of hepatitis C results in improvement in liver stiffness and laboratory liver function tests at 1 year follow-up. In contrast, median COMP-levels remain unchanged during the study period. We conclude that the biomarker potential of COMP in the prospective evaluation of liver diseases, remains to be elucidated.     

Altered serum level of cartilage oligomeric matrix protein and its association with coronary calcification in patients with coronary heart disease

Background Cartilage oligomeric matrix protein (COMP) is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease (CHD) patients, and the relationship between serum COMP and the calcification of coronary artery. Methods A total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed tomography (MSCT) within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages: CHD group (diameter narrowing ≥ 50%, n = 194) and control group (diameter narrowing < 50%, n = 39). The Gensini score, Syntax score and coronary artery calcium score (CACs) were calculated. The serum COMP level was determined using ELISA. Results The levels of COMP were significantly higher in the CHD group than in the control group 155.7 (124.5–194.5) ng/mL vs. 128.4 (113.0–159.9) ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis > 50%. The serum COMP was correlated with age (r = 0.294, P < 0.001), fasting glucose (r = 0.163, P = 0.015), HbA1c (r = 0.194, P = 0.015) and CACs (r = 0.137, P = 0.037). Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients (β = 0.402, t = 2.612, P = 0.015; β = 0.472, t= 3.077, P = 0.005). Performance of COMP for predicting CHD was shown as area under curve (AUC): 0.632, 95% CI: 0.549–0.715 and upper tertile CACs was AUC: 0.602, 95% CI: 0.526–0.678 in receiver operating characteristic (ROC) curve analysis. Conclusion Calcification of coronary artery was an independent predictor of serum COMPs.     

Persistent high serum levels of cartilage oligomeric matrix protein in a subgroup of patients with traumatic knee injury

The objective was to assess whether changes of cartilage oligomeric matrix protein (COMP) serum levels can predict the development of osteoarthritis following traumatic knee injury. Sera and synovial fluids were acquired at surgery (T0) and postoperatively during the first (T1) and second (T2) year from 30 knee-injured patients. COMP levels and anti-COMP autoantibodies were quantified by ELISA. Radiographs and patient questionnaires were used to assess outcomes. At T0, compared with controls (1.6±1.6 μg/ml), the serum COMP concentration was significantly elevated (6.5±2.8 μg/ml) with a tendency to further increase (T0 vs. T1, P=0.076) and subsequently decrease (T1 vs. T2, P=0.074). However, individual variations are observed, e.g. persistently high (8/30) or increasing (T0 to T2, 8/30) serum COMP. Ten of these patients have elevated COMP at T2 that increased from T0. COMP levels in serum and synovial fluid correlated significantly (P=0.012). Interestingly, some patients who revealed increasing serum levels of COMP from T0 to T2 displayed anti-COMP autoantibodies. These data suggest that local immune response could contribute to further joint damage. The subgroup of 10 patients (33%) with elevated and increasing serum COMP levels and in particular the patients with antibodies against cartilage matrix molecules appear at increased risk for developing posttraumatic osteoarthritis. Received: 27 August 1997 / Accepted: 2 March 1998     

布洛芬与氨基葡萄糖对膝骨关节炎患者滑膜细胞增殖及软骨寡聚基质蛋白表达影响的比较

目的 探讨布洛芬与氨基葡萄糖对膝骨关节炎(OA)滑膜细胞增殖及软骨寡聚基质蛋白(COMP)表达的影响.方法 布洛芬与氨基葡萄糖含药血清培养早期和晚期滑膜细胞,四唑氮化合物/黄嘌呤氧化酶(MTS/PMS)法测定吸光度(A)值,hCOMP定量试剂盒测定COMP含量.采用等方差假设双侧t检验进行统计学处理.结果 通过MTS/PMS法观察确定布洛芬与氨基葡萄糖含药血清培养滑膜细胞观察点在第5～7天;氨基葡萄糖含药血清培养滑膜细胞A值[晚期组(0.054±0.021),早期组(0.777±0.034)]低于正常血清对照组(P＜0.05).布洛芬[晚期组(35.4±1.9),早期组(46.0±2.2)]与氨基葡萄糖含药血清[晚期组(36.6±1.3),早期组(48.8±1.3)]对软骨寡聚基质蛋白的表达也有明显降低作用(P＜0.05).结论 氨基葡萄糖可以抑制体外培养早期和晚期膝OA患者滑膜细胞增殖,而布洛芬与氨基葡萄糖皆可抑制体外培养滑膜细胞分泌COMP.     

Dermatan sulfate in the synovial fluid of patients with knee osteoarthritis

Biochemical factors play an important role in osteoarthritis (OA) pathogenesis. The purpose of this study is to clarify whether the dermatan sulfate (DS) levels in the synovial fluid of patients with knee OA are related to residual cartilage. Synovial fluid was obtained from 51 OA patients. Knee radiographs were evaluated with the Kellgren–Lawrence (K/L) grading scale. The levels of the following disaccharides were measured by high-performance liquid chromatography (HPLC): DS (DSΔDi4S), chondroitin 6-sulfate (CSΔDi6S), and chondroitin 4-sulfate (CSΔDi4S). The concentration of cartilage oligomeric matrix protein (COMP) was measured by a sandwich ELISA. The levels of DSΔDi4S in Grades 0 and I OA were significantly higher than levels in Grade II (P = 0.0458), Grade III (P < 0.0001) and Grade IV (P < 0.0001), and we found strong relationships between the levels of DSΔDi4S and those of CSΔDi6S (P < 0.0001, r = 0.705), CSΔDi4S (P < 0.0001, r = 0.750), and COMP (P < 0.0001, r = 0.699). We conclude that the presence of DSΔDi4S reflects proteoglycan metabolism in the residual articular cartilage of OA patients. This suggests that metabolism of the small leucine-rich repeat proteoglycans decorin and biglycan, which contain chains of DSΔDi4S, is similar to that of aggrecan.     

类风湿关节炎患者血清软骨寡聚基质蛋白水平及意义的研究

目的 探讨检测软骨寡聚基质蛋白(COMP)水平对类风湿关节炎(RA)患者疾病活动性及早期软骨破坏的临床意义.方法 采用酶联免疫吸附试验(ELISA)法,检测94例RA患者及40名健康人血清中COMP的水平.同时测定RA患者的其他实验室及临床指标:类风湿因子(RF)、红细胞沉降率(ESR)、C反应蛋白(CRP)、抗环瓜氨酸肽抗体(抗CCP抗体)、压痛关节数、疼痛关节数、肿胀关节数、晨僵时间及双手X线,分析它们与COMP的相关性.结果 RA患者血清COMP水平(11.3±5.2)U/L明显高于正常对照组的(9.2±1.7)U/L;两组差异有统计学意义(p=0.017).64例RA活动期患者血清COMP水平为(14±6)U/L,30例缓解期患者为(9±4)U/L,组间比较差异有统计学意义(p=0.005).COMP水平与RA思者的ESR、CRP、晨僵时间、压痛关节数、疼痛关节数、肿胀关节数、X,线分期呈正相关(P<0.05),与年龄、病程、RF、抗CCP抗体水平、功能分级无明显关系(p＞0.05).30例RA患者完成2年放射学随访,18例COMP值大于健康者,16例X线有递增现象,2例无递增现象;而12例COMP值正常/低于健康者,有递增5例,无递增7例,两组间差异有统计学意义(p=0.013).结论 RA患者血清中COMP高水平存在提示RA疾病活动性和早期关节软骨破坏.COMP可以作为反映RA疾病急性活动程度与软骨破坏的血清学指标.     

Serum levels of cartilage oligomeric matrix protein (COMP): a rapid decrease in patients with active rheumatoid arthritis undergoing intravenous steroid treatment

To examine the influence of intravenous steroid-treatment (IST) on serum levels of Cartilage oligomeric matrix protein (COMP) in patients with active rheumatoid arthritis (RA). Serum levels of COMP and C-reactive protein (CRP) were measured in 12 patients with highly active RA (Steinbrocker stages II–IV) and in 5 patients with highly active reactive arthritis (ReA) (positive testing for HLA-B27) before starting daily IST. Patients received a total steroid dosage between 100 and 500 mg of prednisolone. COMP was measured by a commercially available sandwich-type ELISA-kit developed by AnaMar Medical AB, Sweden. Statistical evaluation was calculated by paired t test. In the RA group, COMP levels ranged from 6.3 to 19.4 U/l (mean 12.9 U/l), CRP from 5 to 195 mg/l (mean 77.8 mg/l), the COMP levels of the ReA group ranged from 5.1 to 7.4 U/l (mean 7.9 U/l), the CRP levels from 13 to 126 mg/l (mean 49 mg/l). We found a significant difference between the initial COMP levels in RA+ and ReA patients (P<0.005). In contrast to the ReA group, serum-COMP levels of RA+ patients (P<0.004) and the VAS (P<0.0001) decreased significantly within 2–10 days after the first treatment with steroids. The CRP levels remained unchanged in both groups. Our results indicate that the intravenous treatment with steroids in patients with highly active RA leads to a significant decrease of cartilage degradation. COMP seems to be a valuable parameter not even as a prognostic factor, but as a marker for monitoring the therapy response in patients with RA.     

The combination of the biomarkers urinary C‐terminal telopeptide of type II collagen,serum cartilage oligomeric matrix protein,and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathy

Objective

Hemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers.

Methods

Blood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C‐terminal telopeptide of type I collagen (CTX‐I), urinary CTX‐II, serum CTX‐I, serum CTX‐II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS‐846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy.

Results

Urinary CTX‐II, serum C1,2C, and serum CS‐846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX‐II, serum COMP, and serum CS‐846. Bone‐specific markers (urinary/serum CTX‐I and serum C1,2C) did not correlate with specific bone‐related items of the Pettersson score (osteoporosis and erosions).

Conclusion

These results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX‐II, serum COMP, and serum CS‐846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage.

     

氨基葡萄糖对体外培养人软骨和滑膜细胞软骨寡聚基质蛋白分泌影响的比较

目的 比较氨基葡萄糖对体外培养软骨和滑膜细胞软骨寡聚基质蛋白(COMP)分泌的影响.方法 软骨细胞和滑膜细胞采自骨关节炎(OA)患者,采用分阶段酶消化法体外培养人软骨细胞和滑膜细胞,给予实验兔以氨基葡萄糖临床等效剂量灌胃后,抽取含药血清培养细胞.采用酶联免疫吸附试验(ELISA)检测药物对体外培养的人软骨细胞和滑膜细胞培养上清液中COMP的浓度.结果 体外培养滑膜细胞分泌的COMP浓度[(41.6±0.4)ng/ml]显著高于软骨细胞[(5.5±3.0)ng/ml](19＜0.05).氨基葡萄糖可显著增加体外培养软骨细胞的COMP分泌[(20.3±3.6)与(5.5±3.0)ng/ml,P＜0.05];而对体外培养滑膜细胞的作用较弱,可轻度减少COMP分泌[(36.6±1.3)与(41.6±0.4)ng/ml].结论 氨基葡萄糖含药血清可以促进体外培养软骨细胞分泌COMP,而对体外培养滑膜细胞无明显作用.     

Radiological and orthopedic score in pediatric hemophilic patients with early and late prophylaxis

 In order to evaluate joint alteration, 17 patients with hemophilia A and B were investigated over a period of 4 years (1993–1997). Patients were subdivided into two groups, according to therapy regimens. In group 1 (n=10) prophylactic treatment was initiated until the third year of life. In group 2 (n=7) patients received prophylactic treatment at the age of 5 years and above. To assess alterations in knee, elbow, and ankle joints, the radiological score and the physical examination score of the Orthopedic Advisory Committee of the World Federation of Hemophilia were used. The sum of the scores of these six joints was defined as the patient-dependent score. Patients of group 1 (median age at the end of observation: 10 years) reached a median radiological score of 1.0 (range: 0–13) and an orthopedic score of 0 (range: 0–4), whereas patients of group 2 (median age: 14 years) had a radiological score of 20 (range: 2–47) and an orthopedic score of 8 (range: 0–12), which shows a significant difference (p<0.01). In both treatment groups a manifestation or progression of arthropathic alteration was seen in those children who had repeated joint bleeding (>5) prior to the onset of prophylactic treatment (r=0.90, p>0.01). Altogether, two of 60 joints in group 1 and 12 of 42 joints in group 2 had a radiological score ≥4. Elbow joints were more often affected than knee and ankle joints. In conclusion, the number of joint bleedings before prophylactic treatment was started influenced the progression of arthropathy even in patients with early onset of prophylaxis. The aim of treatment in severe hemophilia should be early prophylaxis before repeated joint bleeding occurs in order to prevent osteoarthropathic alteration. Received: April 21, 1998 / Accepted: July 2, 1998     

Serum 25-hydroxy vitamin D levels in Egyptian patients with rheumatoid arthritis: Association with disease activity,functional disability and radiological damage

Aim of the workThe aim of this study was to examine vitamin D (VD) levels and its associations with disease activity, functional disability and radiological damage in Egyptian patients with RA.Patients and methodsThis study included 150 RA patients and 150 matched controls. All participants were not receiving VD supplements. Serum 25(OH)-D levels were measured in all participants. Serum 25(OH)-D levels at 30 and 20 ng/ml were the cut-off values for VD insufficiency and deficiency, respectively. Associations of 25(OH)-D levels with disease activity score associated with C-reactive protein (DAS-28-CRP), functional disability assessed by the Health Assessment Questionnaire (HAQ) and radiological damage as assessed by the modified Larsen method were considered.ResultsLow VD levels were frequent in RA patients (22 ± 9.2 ng/ml) compared to the control (28.7 ± 9.6 ng/ml) (p < 0.001); 42.7% had VD levels <20 ng/ml and was <30 ng/ml in 80.7%. RA patients with VD deficiency were older, more frequently females and had higher swollen joint count (SJC), tender joint count, visual analogue scale for pain and DAS28-CRP. Only SJC and DAS28-CRP remained significant following the multivariate analysis (p = 0.029, p = 0.007 respectively), while rheumatoid factor, anti-cyclic citrullinated peptide antibodies, medications used, HAQ and radiologic score had no association with VD levels.ConclusionsVitamin D insufficiency and deficiency are common among Egyptian RA patients and are associated with decreased sun exposure. VD deficiency was related to older age, female gender, swollen joint count and disease activity. Vitamin D levels had no relation with RA functional disability and radiological damage.     

Clinical significance of serum survivin in rheumatoid arthritis patients: Relation to disease activity,functional status and radiological damage

Aim of the workTo measure the levels of serum survivin in rheumatoid arthritis (RA) patients and to assess its relation to disease activity, functional impairment, and radiological damage.Patients and methodsThis study included 58 RA patients and 34 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), modified Larsen radiological score and serum survivin level were assessed.ResultsThe mean age of the patients was 43.5 ± 11.5 years; 43 females and 15 males (F:M 2.9:1) with a mean disease duration of 2.6 ± 1.13 years. RF was positive in 79% Survivin level was significantly increased in patients compared to the controls (171.8 ± 74.4 pg/ml vs. 98.7 ± 16 pg/ml, p < 0.001) and in those with activity (203.1 ± 69.1 pg/ml) compared to those in remission (102.1 ± 12.1 pg/ml). Survivin level tended to be higher in females (177.1 ± 79.5 pg/ml) compared to males (156.4 ± 57 pg/ml) (p = 0.36) and was significantly higher in those with positive RF (183 ± 75.9 pg/ml) compared to those with a negative test (128.6 ± 50.5 pg/ml) (p = 0.02). A significant correlation was detected between survivin and disease duration, DAS28, ESR, CRP, VAS, HAQ, RF, and modified Larsen scores (p < 0.001). On univariate logistic regression the RF, HAQ, modified Larsen and survivin level were significant predictors but were insignificant on multivariate analysis.ConclusionIn RA patients the serum survivin is significantly increased compared to the controls. The disease activity, functional impairment, and radiological joint damage were associated with these high concentrations.