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NMR-based metabolomic approach to study urine samples of chronic inflammatory rheumatic disease patients

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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.

NMR-based metabolomic approach as a tool to study urine samples in CIRD patients with respect to MS patients and healthy controls

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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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    Authors and Affiliations

    1. Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi, 50019, Sesto Fiorentino, Italy

      Alessia Vignoli & Claudio Luchinat

    2. Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

      Donatella Maria Rodio, Elena Anzivino, Monica Mischitelli, Maria Rosa Ciardi, Marco Iannetta & Valeria Pietropaolo

    3. Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci Bolognetti Foundation, Sapienza University of Rome, Viale Regina Elena 291, 00161, Rome, Italy

      Anna Bellizzi

    4. Institute of Chemical Methodologies, “Annalaura Segre” Magnetic Resonance Laboratory, CNR, Via Salaria Km 29,300, 00015, Monterotondo, Italy

      Anatoly Petrovich Sobolev, Donatella Capitani & Luisa Mannina

    5. FiorGen Foundation, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Italy

      Leonardo Tenori

    6. Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

      Federico Marini

    7. Department of Internal Medicine and Medical Specialties, Rheumatology Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

      Roberta Priori, Rossana Scrivo & Guido Valesini

    8. Department of Neurology and Psychiatry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

      Ada Francia & Manuela Morreale

    9. Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

      Cristiana Campanella & Luisa Mannina

    10. Department of Chemistry, University of Florence, Via della Lastruccia, 3-13, 50019, Sesto Fiorentino, Italy

      Claudio Luchinat

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    1. Alessia Vignoli
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    Corresponding author

    Correspondence to Guido Valesini.

    Ethics declarations

    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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    The authors declare that they have no competing interests.

    Additional information

    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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