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Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study

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Abstract

Background

Seronegative elderly-onset rheumatoid arthritis (EORA)neg and polymyalgia rheumatica (PMR) have similar clinical characteristics making them difficult to distinguish based on clinical features. We hypothesized that the study of serum metabolome could identify potential biomarkers of PMR vs. EORAneg.

Methods

Arthritis in older adults (ARTIEL) is an observational prospective cohort with patients older than 60 years of age with newly diagnosed arthritis. Patients’ blood samples were compared at baseline with 18 controls. A thorough clinical examination was conducted. A Bruker Avance 600 MHz spectrometer was used to acquire Nuclear Magnetic Resonance (NMR) spectra of serum samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification.Student t-test, one-way ANOVA, binary linear regression and ROC curve, Pearson’s correlation along with pathway analyses were conducted.

Results

Twenty-eight patients were diagnosed with EORAneg and 20 with PMR. EORAneg patients had a mean disease activity score (DAS)-Erythrocyte Sedimentation Rate (ESR) of 6.21 ± 1.00. All PMR patients reported shoulder pain, and 90% reported pelvic pain. Fifty-eight polar metabolites were identified. Of these, 3-hydroxybutyrate, acetate, glucose, glycine, lactate, and o-acetylcholine (o-ACh), were significantly different between groups. Of interest, IL-6 correlated with different metabolites in PMR and EORAneg suggesting different inflammatory activated pathways. Finally, lactate, o-ACh, taurine, and sex (female) were identified as distinguishable factors of PMR from EORAneg with a sensitivity of 90%, specificity of 92.3%, and an AUC of 0.925 (p < 0.001).

Conclusion

These results suggest that EORAneg and PMR have different serum metabolomic profiles that might be related to their pathobiology and can be used as biomarker to discriminate between both diseases.

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Data Availability

The datasets of metabolites generated during the current study are available from the corresponding author on reasonable request. All data generated or analyzed during this study are included in this published article and its supplementary information files.

Abbreviations

PMR:

Polymyalgia Rheumatica

EORAneg :

Seronegative Elderly Onset Rheumatoid Arthritis. TMAO:Trimethylamine N-Oxide

SG3PC:

Sn-Glycero-3-Phosphocholine. R:Responder

NR:

Non-Responder. DM:Diabetes Mellitus

HTA:

Hypertension

DLP:

Dyslipidemia

BMI:

Body Mass Index. ESR:Erythrocyte Sedimentation Rate

CRP:

C-Reactive protein

IL-6:

Interleukin-6

CRP:

C-Reactive Protein. NSAIDs:Non-Steroidal Anti-Inflammatory Drugs. HAQ:Health Assessment Questionnaire. ANOVA:Analysis of Variance

O-PLSDA:

Orthogonal Partial Least-Squares Discriminant Analysis

VIP:

Variable Importance in Projection

AUC:

Area Under the Curve. 1 H-NMR:Hydrogen-Nuclear Magnetic Resonance.

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Institutes of Health (R01AR073324 to M.G., T32AR064194 to JDM-S and RC).

Author information

Authors and Affiliations

  1. Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA

    Martha Cedeno, Jessica Murillo-Saich, Roxana Coras, Francesca Cedola & Monica Guma

  2. Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, Bellaterra, Barcelona, 08193, Spain

    Roxana Coras & Monica Guma

  3. Department of Rheumatology, Germans Trias i Pujol, University Hospital, Carretera de Canyet, Badalona, 08916, Spain

    Anahy Brandy, Agueda Prior, Lourdes Mateo & Melania Martinez-Morillo

  4. Swedish NMR Centre, University of Gothenburg, Gothenburg, 41390, Sweden

    Anders Pedersen

  5. VA Healthcare Service, San Diego, CA, 92161, USA

    Monica Guma

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Contributions

Supervision of overall project: MG, MM. Conception of design: MG. Patient recruitment: MM, AB, AP, LM. Sample collection: AB, AP, LM, MM. Acquisition of 1 H-NMR data: AP. Analysis: JDM-S, MC, FC, RC. Interpretation of results: JDM-S, MC, RC, FC, LM, MM, MG. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Melania Martinez-Morillo or Monica Guma.

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Ethics approval and consent to participate

The study was approved by the Institutional Board Review at Clinic of the Hospital Universitari Germans Trias i Pujol with the number IP-13-001. All procedures performed in this study were in accordance with the ethical standards of the Institutional Board Review at Clinic of the Hospital Universitari Germans Trias i Pujol and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Not applicable.

Competing interests

All the authors declare that they have no competing interest.

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Cedeno, M., Murillo-Saich, J., Coras, R. et al. Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study. Metabolomics 19, 37 (2023). https://doi.org/10.1007/s11306-023-02004-y

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