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.
机构:
Sanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Kumar, Sandeep
Rawat, Atul
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Ctr Biomed Res, Lucknow, Uttar Pradesh, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Rawat, Atul
Chaurasia, Smriti
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Sanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Chaurasia, Smriti
Kumar, Umesh
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Ctr Biomed Res, Lucknow, Uttar Pradesh, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Kumar, Umesh
Zanwar, Abhishek
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Sanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Zanwar, Abhishek
Dubey, Durgesh
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Ctr Biomed Res, Lucknow, Uttar Pradesh, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Dubey, Durgesh
Goel, Ruchika
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Christian Med Coll & Hosp, Rheumatol, Vellore, Tamil Nadu, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Goel, Ruchika
Danda, Debashish
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Christian Med Coll & Hosp, Clin Immunol & Rheumatol, Vellore, Tamil Nadu, IndiaSanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
Danda, Debashish
Bacon, Paul
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机构:Sanjay Gandhi Postgrad Med Sci, Clin Immunol, Lucknow, Uttar Pradesh, India
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Univ Washington, Northwest Metabol Res Ctr, Anesthesiol & Pain Med, Seattle, WA 98195 USAUniv Washington, Northwest Metabol Res Ctr, Anesthesiol & Pain Med, Seattle, WA 98195 USA
Gowda, G. A. Nagana
Raftery, Daniel
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Univ Washington, Northwest Metabol Res Ctr, Anesthesiol & Pain Med, Seattle, WA 98195 USA
Univ Washington, Dept Chem, Seattle, WA 98195 USA
Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USAUniv Washington, Northwest Metabol Res Ctr, Anesthesiol & Pain Med, Seattle, WA 98195 USA
Raftery, Daniel
CANCER METABOLOMICS: METHODS AND APPLICATIONS,
2021,
1280
: 19
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37
机构:
New Zealand Inst Plant & Food Res Ltd, Biol Chem & Bioact Grp, Auckland, New ZealandUniv Paris Saclay, Dept Med & Technol Sante DMTS, CEA, INRAE, Gif Sur Yvette, France
Pinu, Farhana R.
van der Hooft, Justin J. J.
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Wageningen Univ & Res, Bioinformat Grp, Wageningen, NetherlandsUniv Paris Saclay, Dept Med & Technol Sante DMTS, CEA, INRAE, Gif Sur Yvette, France
van der Hooft, Justin J. J.
Moco, Sofia
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Vrije Univ Amsterdam, Mol & Computat Toxicol Chem & Pharmaceut Sci Dept, AIMMS, Amsterdam, NetherlandsUniv Paris Saclay, Dept Med & Technol Sante DMTS, CEA, INRAE, Gif Sur Yvette, France