Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis

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 lipi...

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Main Authors: Souto-Carneiro, Maria Margarida (Author) , Könyves-Tóth, Lilla (Author) , Behnisch, Rouven (Author) , Urbach, Konstantin (Author) , Klika, Karel D. (Author) , Carvalho, Rui de Albuquerque (Author) , Lorenz, Hanns-Martin (Author)
Format: Article (Journal)
Language:English
Published: 20 February 2020
In: Annals of the rheumatic diseases
Year: 2020, Volume: 79, Issue: 4, Pages: 499-506
ISSN:1468-2060
DOI:10.1136/annrheumdis-2019-216374
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/annrheumdis-2019-216374
Verlag, lizenzpflichtig, Volltext: https://ard.bmj.com/content/79/4/499
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Author Notes:Margarida Souto-Carneiro, Lilla Tóth, Rouven Behnisch, Konstantin Urbach, Karel D. Klika, Rui A. Carvalho, Hanns-Martin Lorenz
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Summary: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.
Item Description:Gesehen am 11.01.2021
Physical Description:Online Resource
ISSN:1468-2060
DOI:10.1136/annrheumdis-2019-216374