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Characterization of nitrotyrosine as a biomarker for arthritis and joint injury

机译：硝基酪氨酸作为关节炎和关节损伤的生物标志物的表征

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Objectives: To characterize the utility of nitrotyrosine (NT) as a biomarker for arthritis and joint injury. Design: Synovial fluid, plasma, and urine from patients diagnosed with osteoarthritis (OA), rheumatoid arthritis (RA), anterior cruciate ligament (ACL) injury, meniscus injury and pseudogout, and knee-healthy volunteers were analyzed for concentrations of NT, nitrate and nitrite (NOx), matrix metalloproteinase (MMP)-3, MMP-1, MMP-9, more than 40 chemokines and cytokines. Results: In OA, plasma and synovial fluid NT were increased versus healthy volunteers. Synovial fluid to plasma NT ratios were elevated in OA patients. Synovial fluid from patients with ACL and meniscus injury and pseudogout had increased levels of NT (P 0.001). In these samples, NT levels significantly correlated with ARGS-aggrecan neoepitope generated by aggrecanase cleavage of aggrecan (P ≤ 0.001), cross-linked C-telopeptides of type II collagen (P 0.001), MMP-1 (P = 0.008), and MMP-3 (P ≤ 0.001). In RA, plasma NT decreased following 6 months of anti-tumor necrosis factor (TNF) treatment. For every 1.1% change in log10 NT, there was a 1.0% change in the log10 disease activity scores (DAS28-3 CRP). Both predicted and observed DAS28-3 CRP showed a robust linear relationship with NT. RA plasma NT positively correlated with CRP, MMP-3 and interferon γ-induced protein 10. Conclusions: NT may serve as a useful biomarker for arthritis and joint injury. In RA, NT is highly correlated with several biomarkers and clinical correlates of disease activity and responds to anti-TNF therapy.
机译：目的：表征硝基酪氨酸（NT）作为关节炎和关节损伤的生物标志物的用途。设计：对诊断为骨关节炎（OA），类风湿性关节炎（RA），前交叉韧带（ACL）损伤，半月板损伤和假痛风的患者以及膝盖健康志愿者的滑液，血浆和尿液进行了NT，硝酸盐浓度分析亚硝酸盐（NOx），基质金属蛋白酶（MMP）-3，MMP-1，MMP-9、40多种趋化因子和细胞因子。结果：与健康志愿者相比，在OA中血浆和滑液NT升高。在OA患者中，滑液与血浆NT的比率升高。来自ACL，半月板损伤和假痛风患者的滑液的NT水平升高（P <0.001）。在这些样品中，NT水平与由蛋白聚糖的蛋白聚糖酶切割产生的ARGS-aggrecan新表位显着相关（P≤0.001），II型胶原的交联C-端肽（P <0.001），MMP-1（P = 0.008），和MMP-3（P≤0.001）。在RA中，经过6个月的抗肿瘤坏死因子（TNF）治疗，血浆NT下降。 log10 NT的每变化1.1％，log10疾病活性评分（DAS28-3 CRP）就会变化1.0％。预测和观察到的DAS28-3 CRP均与NT表现出稳健的线性关系。 RA血浆NT与CRP，MMP-3和干扰素γ诱导的蛋白10呈正相关。结论：NT可能是关节炎和关节损伤的有用生物标志物。在RA中，NT与多种生物标志物和疾病活动的临床相关性高度相关，并对抗TNF治疗有反应。

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