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

Abstract

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.

Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment

“…A larger study, conducted by Jain et al in another cohort, confirmed these results and confirmed the role of glutamate and NAG as potentially strong biomarkers of TA [129].…”

“…Takayasu arteritis N-Acetyl glycoproteins are significantly up-regulated in TA patients [129,130] Kawasaki disease High levels of GlycA were confirmed in paediatric population with acute KD disease [110]…”

Biomarkers in Vasculitides of the Nervous System

“…Nuclear Magnetic Resonance Spectroscopy (NMR) based serum metabolomics has identified distinct profiles in individuals suffering from TA in comparison to age- and sex-matched controls (56). The best discriminatory potential was found for N-acetyl glycoprotein (NAG), an anti-inflammatory metabolite, and glutamate, a neurotransmitter often associated with inflammation (56–58). Upon follow up, changes in metabolic spectra evolved with a change in disease activity.…”

“…Upon follow up, changes in metabolic spectra evolved with a change in disease activity. Thus, certain metabolic profiles allow the distinction between clinically active and inactive TA patients, representing potential biomarkers for disease activity and delivering additional information which can serve as a guide to therapy (56). Future studies should further investigate these findings in larger cohorts with a longer follow up duration.…”

A comparative analysis of different biofluids using Raman spectroscopy to determine disease activity in ANCA‐associated vasculitis

“…A limited number of studies have successfully applied metabolomics as a potential candidate biomarker for disease activity in vasculitis. Its use in Takyasu's arteritis (TA) has been evaluated, demonstrating good ability to distinguish active from quiescent disease, with acute phase protein associated N‐acetyl glycoprotein (NAG) as the key discriminating metabolite [22,23]. Al‐Ani et al analysed the urinary metabolomic profile in cases of renal limited AAV, demonstrating good discriminatory capacity with hypocitraturia and raised levels of myo‐inositol associating with active disease [24].…”