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Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis
  1. Margarida Souto-Carneiro1,
  2. Lilla Tóth1,2,
  3. Rouven Behnisch3,
  4. Konstantin Urbach1,
  5. Karel D Klika4,
  6. Rui A Carvalho1,5,
  7. Hanns-Martin Lorenz1
  1. 1 Medizin 5, Hämatologie, Onkologie und Rheumatologie, UniversitätsKlinikum Heidelberg, Heidelberg, Germany
  2. 2 Internal Medicine, Semmelweis University of Medicine, Budapest, Hungary
  3. 3 Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany
  4. 4 Department of Molecular and Structural Biology, German Cancer Research Centre, Heidelberg, Germany
  5. 5 Department of Life Sciences, University of Coimbra Faculty of Sciences and Technology, Coimbra, Portugal
  1. Correspondence to Dr Margarida Souto-Carneiro, Medizin 5, Hämatologie, Onkologie und Rheumatologie, UniversitätsKlinikum Heidelberg, Heidelberg 69120, Germany; margarida.souto-carneiro{at}


Objectives The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases.

Methods Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort. Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model.

Results Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%. Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified.

Conclusions PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.

  • differential diagnosis
  • seronegative arthritis
  • metabolomics
  • lipidomics
  • psoriatic arthritis

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  • RAC and H-ML are joint senior authors.

  • Handling editor Josef S Smolen

  • LT and RB contributed equally.

  • Contributors Conceptualisation: MS-C, RAC and H-ML; methodology: MS-C, RAC, KDK and RB; formal analysis: LT, RB, KU, MS-C and RAC; investigation: LT, KU and KDK; resources: H-ML, MS-C, RAC and KDK; writing – original/ draft: LT, RB, KU, H-ML, MS-C, KDK and RAC; writing – review and editing: RB, MS-C, RAC, H-ML and KDK; supervision: MS-C, RAC and H-ML; funding acquisition: MS-C, RAC and H-ML.

  • Funding LT was funded by a Jellinek Harry Scholarship EFOP-3.63-VEKOP-16-2017-00009 (Az orvos-, egészségtudományi és gyógyszerészképzés tudományos műhelyeinek fejlesztése). This work was supported by a grant of the German Research Foundation (Deutsche Forschungsgesellschaft) to MM Souto-Carneiro SO 1402/1-1.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Original NMR spectra files are available on reasonable and justified request. Please contact the corresponding author.

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