Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA.

Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA.
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DOI:
10.1016/j.joca.2012.05.003
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发表时间:
2012-08
影响因子:
7
通讯作者:
Liu, C. J.
Liu, C. J.
中科院分区:
医学2区
文献类型:
--
作者:
Lai, Y.;Yu, X-P.;Zhang, Y.;Tian, Q.;Song, H.;Mucignat, M. T.;Perris, R.;Samuels, J.;Krasnokutsky, S.;Attur, M.;Greenberg, J. D.;Abramson, S. B.;Di Cesare, P. E.;Liu, C. J.

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本研究旨在确定COMP降解产物的评估是否可作为关节炎的血清学病程和治疗反应预测因子。我们产生了一组针对COMP片段的单克隆抗体,并开发了一种新的捕获ELISA用于检测骨关节炎(OA)和类风湿性关节炎(RA)患者的COMP片段。该试验还用于监测手术诱导的OA、胶原诱导的关节炎(CIA)和TNF转基因动物模型中的COMP片段。与市售COMP ELISA试剂盒检测到的OA和对照组之间COMP水平无显著差异相比,该新建立的ELISA检测的OA患者血清中COMP片段显著增加。此外,血清COMP片段水平与OA患者的严重程度和小鼠模型中手术诱导的OA的进展密切相关。此外,RA患者、CIA小鼠和TNF转基因小鼠的血清COMP片段水平显著高于其对照组。有趣的是,TNFα抑制剂和甲氨蝶呤治疗导致RA患者血清COMP片段显著减少。另外,Atsttrin的施用(Tang等人,Science,2011 332(6028):478)也导致关节炎小鼠模型中COMP片段的显著减少。一种新的夹心ELISA能够在关节炎患者和啮齿类动物关节炎模型中可重复地测量血清COMP片段。该试验还提供了一种利用血清COMP片段监测关节炎干预效果的有价值的手段。
The study aimed determining whether assessment of COMP degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture ELISA for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically induced OA, collagen induced arthritis (CIA), and TNF transgenic animal models. Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin (Tang, et al, Science, 2011 332(6028):478) also resulted in a significant reduction in COMP fragments in arthritis mice models. A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.
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