NMR-Based Serum Metabolomics of Patients with Takayasu Arteritis: Relationship with Disease Activity

被引:17
|
作者
Jain, Avinash [1 ]
Kumar, Dinesh [2 ]
Guleria, Anupam [2 ]
Misra, Durga Prasanna [1 ]
Zanwar, Abhishek [1 ]
Chaurasia, Smriti [1 ]
Kumar, Sandeep [1 ]
Kumar, Umesh [2 ]
Mishra, Shravan K. [1 ]
Goel, Ruchika [3 ]
Danda, Debashish [3 ]
Misra, Ramnath [1 ]
机构
[1] SGPGIMS, Dept Clin Immunol, Lucknow 226014, Uttar Pradesh, India
[2] Ctr Biomed Res, Lucknow 226014, Uttar Pradesh, India
[3] Christian Med Coll & Hosp, Vellore 632004, Tamil Nadu, India
关键词
Takayasu arteritis; disease activity; ITAS; metabolomics; NMR; BIOMARKER DISCOVERY; INFLAMMATION; ATHEROSCLEROSIS; DIAGNOSIS; CANCER;
D O I
10.1021/acs.jproteome.8b00456
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 analyzed 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], 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.
引用
收藏
页码:3317 / 3324
页数:8
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