Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis. Assessment of disease activity is a challenge and there is an unmet need for relevant biomarker(s). In our previous study, NMR based serum metabolomics had revealed distinctive metabolic signatures in TA patients compared with age/sex matched healthy controls and Systemic Lupus Erythematosus (SLE). In this study, we investigate whether the metabolites correlate with disease activity. Patients with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled and disease activity was assessed using Indian Takayasu Clinical Activity Score using Acute Phase Reactant – Erythrocyte Sedimentation Rate [ITAS-A (ESR]. Sera were analysed using 800 MHz NMR spectrometer to identify metabolites [based on Partial Least Squares Discriminant Analysis (PLS-DA) VIP (variable importance in projection) score >1.0 and permutation test, p-value < 0.01]. 45 active and 53 inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37 years] female to male ratio 3.5:1 and 4.9:1 and median duration of illness 5 [(IQR) 2-9 years] and 3 [(IQR) 1-6 years] years respectively were enrolled. The key metabolites with highest discriminatory potential in active TA (ITAS-A ≥4) were glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the curve 0.775 and 0.769 (p-value<0.001). On follow up assessment, metabolic spectra started to differ with change in disease activity. This large cohort of patients revealed metabolic profiles discriminating between clinically active and inactive TA patients. It suggests glutamate and NAG have strong potential as biomarkers for disease activity in TA and may serve as a guide to therapy. We are now working to further validate these results in longitudinal studies.

中文翻译：

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高筋动脉炎（TA）患者的基于NMR的血清代谢组学-与疾病活动的关系

Takayasu动脉炎（TA）是发病机制未知的大血管血管炎。疾病活动性的评估是一个挑战，对相关生物标志物的需求尚未得到满足。在我们之前的研究中，与年龄/性别匹配的健康对照和系统性红斑狼疮（SLE）相比，基于NMR的血清代谢组学揭示了TA患者独特的代谢特征。在这项研究中，我们调查了代谢产物是否与疾病活动相关。纳入符合美国风湿病学会（ACR）标准的TA患者，并使用印度Takayasu临床活性评分和急性期反应物–红细胞沉降率[ITAS-A（ESR）]评估疾病活动。使用800 MHz NMR光谱仪分析血清以鉴定代谢物[基于偏最小二乘判别分析（PLS-DA）VIP（投影中的重要性变化）得分> 1.0和置换检验，p值<0.01）。45名活跃患者和53名非活跃TA患者，中位年龄为27 [（IQR）22-35岁]和27 [（IQR）23-37岁]，男女之比为3.5：1和4.9：1，中位病程为5 [[ IQR] 2-9岁]和3 [（IQR）1-6岁]年。活性TA（ITAS-A≥4）最具鉴别潜力的关键代谢物是谷氨酸和N-乙酰基糖蛋白（NAG），二者均升高，面积在曲线下（0.775）和0.769（p值<0.001）。在随访评估中，代谢谱随疾病活动的变化而开始不同。大量患者揭示了代谢特征，可区分临床活跃和非活跃TA患者。这表明谷氨酸和NAG作为TA中疾病活动的生物标志物具有很强的潜力，并可作为治疗的指南。我们现在正在努力在纵向研究中进一步验证这些结果。