Centre of Biomedical Research, Lucknow-226014, Uttar Pradesh, India; Department of Zoology, BBAU, Lucknow-226025, India.
Department of Clinical Immunology, SGPGIMS, Raibareli Road, Lucknow-226014, India.
J Pharm Biomed Anal. 2020 Feb 20;180:113080. doi: 10.1016/j.jpba.2019.113080. Epub 2019 Dec 24.
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.
定量评估疾病活动对于 Takayasu 动脉炎（TA）患者的有效治疗至关重要。活性谷氨酰胺分解和糖酵解通量降低是炎症活动的标志。基于此，我们假设循环谷氨酰胺/葡萄糖比（QGR）可以作为 TA 中炎症活动的指标。为了验证这一假设，我们从符合美国风湿病学会（ACR）标准的 45 例活动期和 53 例非活动期 TA 患者中采集血清样本，并根据急性相反应物-红细胞沉降率[TA 临床活动评分（ITAS）-A（ESR）]评估疾病活动。使用高场（800 MHz）NMR 光谱法测量与谷氨酰胺分解（谷氨酰胺和谷氨酸）相关的循环代谢物的定量特征，以及估计糖酵解通量的代谢物（即葡萄糖和乳酸）。使用 CHENOMX NMR 套件分析记录的光谱，并使用 Metaboanalyst 比较和评估估计的浓度谱，以评估其诊断潜力。与非活动期 TA 患者相比，活动期 TA 患者的血清中谷氨酰胺和乳酸水平显著降低，表明这些患者表现出活性谷氨酰胺分解和糖酵解活性降低。这进一步得到了活性 TA 患者 QGR 和乳酸与葡萄糖比（LGR）水平明显低于非活动 TA 患者的支持。受试者工作特征（ROC）曲线分析显示，QGR 的准确性、敏感性和特异性均令人满意[ROC 曲线下面积（AUROC）= 0.76，95%置信区间（CI）= 0.66-0.84]，而 LGR 的 AUROC 为 0.67，CI 为 0.561-0.77。因此，我们认为循环 QGR 有可能作为 TA 患者疾病活动评估的替代标志物。然而，在临床环境中使用该比值需要对大量患者队列进行进一步研究和程序优化，以提高准确性。
