The role of synovial fluid markers of catabolism and anabolism in osteoarthritis, rheumatoid arthritis and asymptomatic organ donors.
The role of synovial fluid markers of catabolism and anabolism in osteoarthritis, rheumatoid arthritis and asymptomatic organ donors.
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DOI：
10.1186/ar3293
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发表时间：
2011-03-24
影响因子：
4.9
通讯作者：
Chubinskaya S
中科院分区：
文献类型：
--
作者：
Kokebie R;Aggarwal R;Lidder S;Hakimiyan AA;Rueger DC;Block JA;Chubinskaya S
本研究的目的是将类风湿性关节炎（RA）患者、骨关节炎（OA）患者和无症状器官供体的滑液（SF）中合成代谢和分解代谢生物标志物的水平相关联。从45例OA、22例RA患者和20例无症状器官供体的膝关节收集SF。通过酶联免疫吸附试验选择并分析了8种生物标志物：白细胞介素（IL）-1，IL-6，IL-8和IL-11;白血病抑制因子（LIF）;软骨寡聚蛋白（COMP）;骨钙素;和成骨蛋白1（OP-1）。数据表示为中位数（四分位距）。根据西安大略和麦克马斯特大学的OA患者指数评分以及RA患者的白色血细胞计数、红细胞沉降率和C-反应蛋白水平评估性别和疾病活动度的影响。患者的平均年龄（± SD）如下：OA患者为53 ± 9岁，RA患者为54 ± 11岁，无症状器官供体为52 ± 7岁。没有发现参与者性别的影响。在RA患者的SF中，五种细胞因子中有四种高于OA患者和无症状器官供体的SF。发现IL-6和IL-8的差异最显著，其中RA患者SF中的IL-6浓度几乎是OA患者的3倍，是无症状供体对照的4倍：354.7 pg/ml（1，851.6）vs. 119.4 pg/ml（193.2）vs. 86.97 pg/ml（82.0）（分别为P < 0.05和P < 0.05）。RA患者SF中IL-8浓度高于OA患者和无症状供者对照组：583.6 pg/ml（1086.4）vs.429 pg/ml（87.3）vs.451 pg/ml（170.1）（分别为P < 0.05和P < 0.05）。RA患者和OA患者的SF中IL-11无差异，而OA患者和无症状供体对照的SF中检测到1.4倍的差异：296.2 pg/ml（257.2）vs. 211.6 pg/ml（40.8）（P < 0.05）。RA患者SF中IL-1浓度最高（9.26 pg/ml（11.1）），无症状供者SF中IL-1浓度显著高于OA患者（9.083 pg/ml（1.6）vs.7.76 pg/ml（2.6）; P < 0.05）。相反，无症状供体对照样品具有最高的LIF浓度：RA患者SF中的228.5 pg/ml（131.6）vs. 128.4 pg/ml（222.7）vs. OA患者SF中的107.5 pg/ml（136.9）（P < 0.05）。RA患者SF中OP-1浓度是OA患者的2倍，是无症状供体对照样本的3倍（分别为167.1 ng/ml（194.8）vs. 81.79 ng/ml（116.0）vs. 54.49 ng/ml（29.3）; P < 0.05）。两组之间COMP和骨钙素的差异无法区分，活动性和非活动性OA和RA之间的差异也是如此。所选生物标志物的激活对应于驱动每种疾病的机制。IL-11、LIF和OP-1可被视为OA的一组重要生物标志物;而IL-1、IL-6、IL-8、LIF和OP-1的谱分析在RA中可能更重要。需要更大、更好定义的患者队列来开发用于预后的生物标志物算法。
The purpose of this study was to correlate the level of anabolic and catabolic biomarkers in synovial fluid (SF) from patients with rheumatoid arthritis (RA), patients with osteoarthritis (OA) and asymptomatic organ donors. SF was collected from the knees of 45 OA, 22 RA patients and 20 asymptomatic organ donors. Eight biomarkers were selected and analyzed by using an enzyme-linked immunosorbent assay: interleukin (IL)-1, IL-6, IL-8 and IL-11; leukemia-inhibitory factor (LIF); cartilage oligomeric protein (COMP); osteocalcin; and osteogenic protein 1 (OP-1). Data are expressed as medians (interquartile ranges). The effects of sex and disease activity were assessed on the basis of the Western Ontario and McMaster Universities index score for patients with OA and on the basis of white blood cell count, erythrocyte sedimentation rate and C-reactive protein level for patients with RA. The mean ages (± SD) of the patients were as follows: 53 ± 9 years for patients with OA, 54 ± 11 years for patients with RA and 52 ± 7 years for asymptomatic organ donors. No effect of participants' sex was identified. In the SF of patients with RA, four of five cytokines were higher than those in the SF of patients with OA and those of asymptomatic organ donors. The most significant differences were found for IL-6 and IL-8, where IL-6 concentration in SF of patients with RA was almost threefold higher than that in patients with OA and fourfold higher than that in asymptomatic donor controls: 354.7 pg/ml (1,851.6) vs. 119.4 pg/ml (193.2) vs. 86.97 pg/ml (82.0) (P < 0.05 and P < 0.05, respectively). IL-8 concentrations were higher in SF of patients with RA than that in patients with OA as well as that in asymptomatic donor controls: 583.6 pg/ml (1,086.4) vs. 429 pg/ml (87.3) vs. 451 pg/ml (170.1) (P < 0.05 and P < 0.05, respectively). No differences were found for IL-11 in the SF of patients with RA and that of patients with OA, while a 1.4-fold difference was detected in the SF of patients with OA and that of asymptomatic donor controls: 296.2 pg/ml (257.2) vs. 211.6 pg/ml (40.8) (P < 0.05). IL-1 concentrations were the highest in the SF of RA patients (9.26 pg/ml (11.1)); in the SF of asymptomatic donors, it was significantly higher than that in patients with OA (9.083 pg/ml (1.6) vs. 7.76 pg/ml (2.6); P < 0.05). Conversely, asymptomatic donor control samples had the highest LIF concentrations: 228.5 pg/ml (131.6) vs. 128.4 pg/ml (222.7) in the SF of patients with RA vs. 107.5 pg/ml (136.9) in the SF of patients with OA (P < 0.05). OP-1 concentrations were twofold higher in the SF of patients with RA than those in patients with OA and threefold higher than those in asymptomatic donor control samples (167.1 ng/ml (194.8) vs. 81.79 ng/ml (116.0) vs. 54.49 ng/ml (29.3), respectively; P < 0.05). The differences in COMP and osteocalcin were indistinguishable between the groups, as were the differences between active and inactive OA and RA. Activation of selected biomarkers corresponds to the mechanisms that drive each disease. IL-11, LIF and OP-1 may be viewed as a cluster of biomarkers significant for OA; while profiling of IL-1, IL-6, IL-8, LIF and OP-1 may be more significant in RA. Larger, better-defined patient cohorts are necessary to develop a biomarker algorithm for prognostic use.
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影响因子：
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通讯作者：
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INGEMANNHANSEN, T