Analytical and Bioanalytical Chemistry

, Volume 409, Issue 5, pp 1405–1413 | Cite as

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

  • Alessia Vignoli
  • Donatella Maria Rodio
  • Anna Bellizzi
  • Anatoly Petrovich Sobolev
  • Elena Anzivino
  • Monica Mischitelli
  • Leonardo Tenori
  • Federico Marini
  • Roberta Priori
  • Rossana Scrivo
  • Guido ValesiniEmail author
  • Ada Francia
  • Manuela Morreale
  • Maria Rosa Ciardi
  • Marco Iannetta
  • Cristiana Campanella
  • Donatella Capitani
  • Claudio Luchinat
  • Valeria Pietropaolo
  • Luisa Mannina
Research Paper


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.

Graphical abstract

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


Nuclear magnetic resonance spectroscopy Metabolomics Urine Multivariate data analysis Chronic inflammatory rheumatic diseases 



Chronic inflammatory rheumatic diseases


Correlation spectroscopy


Cerebrospinal fluid


Heteronuclear multiple bond correlation


High-performance liquid chromatography


Heteronuclear single quantum coherence


Multiple sclerosis


Nuclear magnetic resonance


Partial least squares-discriminant analysis


Trimethylsilyl propionate


Urinary tract infections


Variable importance in projection



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).

Compliance with ethical standards

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.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

216_2016_74_MOESM1_ESM.pdf (353 kb)
ESM 1 (PDF 352 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Alessia Vignoli
    • 1
  • Donatella Maria Rodio
    • 2
  • Anna Bellizzi
    • 3
  • Anatoly Petrovich Sobolev
    • 4
  • Elena Anzivino
    • 2
  • Monica Mischitelli
    • 2
  • Leonardo Tenori
    • 5
  • Federico Marini
    • 6
  • Roberta Priori
    • 7
  • Rossana Scrivo
    • 7
  • Guido Valesini
    • 7
    Email author
  • Ada Francia
    • 8
  • Manuela Morreale
    • 8
  • Maria Rosa Ciardi
    • 2
  • Marco Iannetta
    • 2
  • Cristiana Campanella
    • 9
  • Donatella Capitani
    • 4
  • Claudio Luchinat
    • 1
    • 10
  • Valeria Pietropaolo
    • 2
  • Luisa Mannina
    • 9
    • 4
  1. 1.Magnetic Resonance Center (CERM)University of FlorenceSesto FiorentinoItaly
  2. 2.Department of Public Health and Infectious DiseasesSapienza University of RomeRomeItaly
  3. 3.Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci Bolognetti FoundationSapienza University of RomeRomeItaly
  4. 4.Institute of Chemical Methodologies, “Annalaura Segre” Magnetic Resonance LaboratoryCNRMonterotondoItaly
  5. 5.FiorGen FoundationSesto FiorentinoItaly
  6. 6.Department of ChemistrySapienza University of RomeRomeItaly
  7. 7.Department of Internal Medicine and Medical Specialties, Rheumatology UnitSapienza University of RomeRomeItaly
  8. 8.Department of Neurology and PsychiatrySapienza University of RomeRomeItaly
  9. 9.Department of Drug Chemistry and TechnologiesSapienza University of RomeRomeItaly
  10. 10.Department of ChemistryUniversity of FlorenceSesto FiorentinoItaly

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