Adams Samuel B, Nettles Dana L, Jones Lynne C, Miller Stuart D, Guyton Gregory P, Schon Lew C
Department of Orthopaedic Surgery, MedStar Union Memorial Hospital, Baltimore, MD, USA.
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Foot Ankle Int. 2014 Dec;35(12):1241-9. doi: 10.1177/1071100714550652. Epub 2014 Sep 8.
There is a paucity of research on posttraumatic ankle arthritis (PTAA). We aimed to identify synovial fluid PTAA biomarkers using cytokine analysis and metabolic profiling.
Ankle joint synovial fluid was obtained from 20 patients with PTAA and 20 patients with no ankle pain and no radiographic evidence of ankle arthritis (control group). Synovial fluid samples were analyzed for IFN-γ, TNF-α, MIP-1β, MCP-1, IL-1β, IL-1Ra, IL-4, IL-6, IL-8, IL-10, IL-13, and IL-15 using ELISA and for more than 3000 metabolites using liquid and gas chromatography with mass spectroscopy. To compare presence of cytokines and metabolites between groups, t tests were used. Random forest analysis was performed on metabolites to determine whether control and PTAA samples could be differentiated based on metabolic profile.
IL-1Ra, IL-6, IL-8, IL-10, IL-15, and MCP-1 were significantly elevated in the PTAA group. In addition, 107 metabolites in the PTAA group were significantly altered, including derangement in amino acid, carbohydrate, lipid, and energy metabolism, extracellular matrix turnover, and collagen degradation. Random forest analysis yielded a predictive accuracy of 90% when using the metabolic profiles to distinguish between control and PTAA samples.
This study identified inflammatory cytokines and metabolites present in the synovial fluid of PTAA.
Several of these entities have previously been implicated in rheumatoid arthritis and osteoarthritis of the knee, but many could potentially be used as novel biomarkers of PTAA. Most importantly, the findings suggest that metabolites could be used to distinguish synovial fluid from patients with PTAA.
关于创伤后踝关节关节炎（PTAA）的研究较少。我们旨在通过细胞因子分析和代谢谱分析确定滑液中PTAA的生物标志物。
从20例PTAA患者和20例无踝关节疼痛且无踝关节关节炎影像学证据的患者（对照组）获取踝关节滑液。使用酶联免疫吸附测定法（ELISA）分析滑液样本中的干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、巨噬细胞炎性蛋白-1β（MIP-1β）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-1β（IL-1β）、白细胞介素-1受体拮抗剂（IL-1Ra）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-13（IL-13）和白细胞介素-15，并使用液相色谱-质谱联用仪和气相色谱-质谱联用仪分析3000多种代谢物。为比较两组间细胞因子和代谢物的存在情况，采用t检验。对代谢物进行随机森林分析，以确定能否根据代谢谱区分对照组和PTAA样本。
PTAA组中白细胞介素-1受体拮抗剂（IL-1Ra）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-15（IL-15）和单核细胞趋化蛋白-1（MCP-1）显著升高。此外，PTAA组中有107种代谢物发生显著改变，包括氨基酸、碳水化合物、脂质和能量代谢紊乱、细胞外基质周转以及胶原蛋白降解。使用代谢谱区分对照组和PTAA样本时，随机森林分析的预测准确率为90%。
本研究确定了PTAA滑液中存在的炎性细胞因子和代谢物。
其中一些物质先前已被认为与类风湿关节炎和膝关节骨关节炎有关，但许多物质可能潜在地用作PTAA的新型生物标志物。最重要的是，研究结果表明代谢物可用于区分PTAA患者的滑液。
