Abstract
The nuclear magnetic resonance (NMR)-based metabolomic approach was used as analytical methodology to study the urine samples of chronic inflammatory rheumatic disease (CIRD) patients. The urine samples of CIRD patients were compared to the ones of both healthy subjects and patients with multiple sclerosis (MS), another immuno-mediated disease. Urine samples collected from 39 CIRD patients, 25 healthy subjects, and 26 MS patients were analyzed using 1H NMR spectroscopy, and the NMR spectra were examined using partial least squares-discriminant analysis (PLS-DA). PLS-DA models were validated by a double cross-validation procedure and randomization tests. Clear discriminations between CIRD patients and healthy controls (average diagnostic accuracy 83.5 ± 1.9%) as well as between CIRD patients and MS patients (diagnostic accuracy 81.1 ± 1.9%) were obtained. Leucine, alanine, 3-hydroxyisobutyric acid, hippuric acid, citric acid, 3-hydroxyisovaleric acid, and creatinine contributed to the discrimination; all of them being in a lower concentration in CIRD patients as compared to controls or to MS patients. The application of NMR metabolomics to study these still poorly understood diseases can be useful to better clarify the pathologic mechanisms; moreover, as a holistic approach, it allowed the detection of, by means of anomalous metabolic traits, the presence of other pathologies or pharmaceutical treatments not directly connected to CIRDs, giving comprehensive information on the general health state of individuals.
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Abbreviations
- CIRDs:
-
Chronic inflammatory rheumatic diseases
- COSY:
-
Correlation spectroscopy
- CSF:
-
Cerebrospinal fluid
- HMBC:
-
Heteronuclear multiple bond correlation
- HPLC:
-
High-performance liquid chromatography
- HSQC:
-
Heteronuclear single quantum coherence
- MS:
-
Multiple sclerosis
- NMR:
-
Nuclear magnetic resonance
- PLS-DA:
-
Partial least squares-discriminant analysis
- TMSP:
-
Trimethylsilyl propionate
- UTIs:
-
Urinary tract infections
- VIP:
-
Variable importance in projection
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Acknowledgements
This study has been developed within the “Unità di Metabolomica: Studi su Alimenti, Nutraceutici e Fluidi biologici” of the Sapienza University of Rome. This work has been partially supported by Fondazione Veronesi that granted L.T. through the Post-Doctoral Fellowship 2015 and by Ateneo 2015 (Sapienza University of Rome prot C26A15CJ98).
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The study received the approval by the local ethics committee in accordance with local requirements, and at the time of the collection, informed consent was obtained from each participant enrolled in the study.
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Alessia Vignoli, Donatella Maria Rodio, Anna Bellizzi and Anatoly Petrovich Sobolev contributed equally to this work.
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Vignoli, A., Rodio, D.M., Bellizzi, A. et al. NMR-based metabolomic approach to study urine samples of chronic inflammatory rheumatic disease patients. Anal Bioanal Chem 409, 1405–1413 (2017). https://doi.org/10.1007/s00216-016-0074-z
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DOI: https://doi.org/10.1007/s00216-016-0074-z