Quantitative assessment of disease activity is important for effective care of patients with Takayasu arteritis (TA). Activated glutaminolysis and reduced glycolytic flux is the hallmark of active inflammation. Based on this, we hypothesize that the circulatory Glutamine/Glucose ratio (QGR) can serve as an indicant of active inflammation in TA. To probe this hypothesis, the serum samples were collected from 45 active and 53 inactive TA patients fulfilling American College of Rheumatology (ACR) criteria and assessed for disease activity according to Indian Takayasu Clinical Activity Score (ITAS) using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. The quantitative profiles of circulatory metabolites implicated in glutaminolysis (Glutamine and Glutamate) and those which estimate glycolytic flux (i.e. glucose and lactate) were measured using high field (800 MHz) NMR spectroscopy. The recorded spectra were analyzed using CHENOMX NMR Suite and the estimated concentration profiles were compared and evaluated for their diagnostic potential using Metaboanalyst. Compared to inactive-TA patients, the sera of active-TA patients were characterized by significantly decreased serum levels of glutamine and lactate suggesting that these patients exhibit activated glutaminolysis and reduced glycolytic activity. This is further supported by significantly decreased QGR and lactate to glucose ratio (LGR) levels in active compared to inactive TA patients. The receiver operating characteristic (ROC) curve analysis revealed satisfactory accuracy, sensitivity and specificity for QGR [with area under ROC curve (AUROC) = 0.76 and 95% confidence interval (CI) = 0.66-0.84) compared to that for LGR (with AUROC = 0.67 and CI = 0.561-0.77). Therefore, we believe that the circulatory QGR has the potential to serve as surrogate marker for the assessment of disease activity in TA patients. However, the use of this ratio in clinical settings will require future studies on large patient cohorts and procedural optimization as well to improve accuracy.

中文翻译：

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循环谷氨酰胺/葡萄糖比，以评估高津市大动脉炎的疾病活动：基于NMR的血清代谢组学研究。

疾病活动性的定量评估对于有效预防Takayasu动脉炎（TA）的患者非常重要。激活的谷氨酰胺分解和降低的糖酵解通量是活动性炎症的标志。基于此，我们假设循环谷氨酰胺/葡萄糖比（QGR）可以作为TA中活动性炎症的指标。为了探究这一假设，从符合美国风湿病学会（ACR）标准的45名活跃和53名非活跃TA患者中收集血清样本，并根据印度Takayasu临床活性评分（ITAS）使用急性期反应物-红细胞沉降率评估疾病活动[ITAS-A（ESR）]。谷氨酰胺分解涉及的循环代谢产物（谷氨酰胺和谷氨酸）的定量曲线和估计糖酵解通量的定量曲线（即 使用高场（800 MHz）NMR光谱仪进行测量。使用CHENOMX NMR Suite分析记录的光谱，并比较估计的浓度曲线，并使用Metaboanalyst评估其诊断潜力。与非活动性TA患者相比，活动性TA患者的血清血清谷氨酰胺和乳酸水平显着降低，这表明这些患者表现出激活的谷氨酰胺分解和降低的糖酵解活性。与非活动性TA患者相比，活动中的QGR和乳酸/葡萄糖比率（LGR）水平显着降低进一步证明了这一点。接收器工作特性（ROC）曲线分析显示出令人满意的QGR准确性，灵敏度和特异性[ROC曲线下面积（AUROC）= 0.76，95％置信区间（CI）= 0。66-0.84）与LGR（AUROC = 0.67和CI = 0.561-0.77）相比。因此，我们认为循环QGR有潜力作为评估TA患者疾病活动的替代指标。但是，在临床环境中使用该比率将需要对大型患者队列和程序优化进行进一步研究，以提高准确性。