The metabolomic profile of psoriatic arthritis patients unveils the unbalance of disease-related molecules and pathways

TL;DR

This study uses metabolomics to identify key metabolic differences in psoriatic arthritis patients compared to healthy controls, revealing disrupted pathways linked to inflammation and metabolism.

Contribution

The study identifies specific metabolite imbalances and enriched metabolic pathways in psoriatic arthritis patients using serum NMR profiling.

Findings

PsA patients showed increased glucose and glycyl proline, and decreased alanine, glutamine, methionine, serine, and branched-chain amino acids.

Metabolomic profiling revealed enriched pathways including glucose-alanine cycle, glycine and serine metabolism, and glutathione metabolism.

Alanine and leucine levels correlated directly with PsA disease activity score (DAPSA).

Abstract

Among the unmet needs in psoriatic arthritis (PsA), the precise mechanisms underlying the contribution of genetic susceptibility, environmental triggers and systemic inflammation are still under investigation. As a complex and multi-factorial condition, metabolomics in PsA may offer additional insight into pathways driving the pathogenesis, allowing for a better understanding of the disease-related variations downstream of the genome and proteome. In this study, the serum metabolomics profile of PsA was compared with healthy controls, by nuclear magnetic resonance spectroscopy (1H-NMR). Twenty-nine PsA patients according to CASPAR criteria and DAPSA > 14 score plus 33 healthy controls matched for mean age and gender ratio, were enrolled. The sera metabolomics profile was analysed with a Varian Unity Inova 500 MHz NMR spectrometer, combined with multivariate statistical analysis (MVA). The MetaboAnalyst program was used to generate ROC curves and to perform the enrichment analysis. The OPLS-DA models exhibited a clear separation between the two groups, and the metabolomic profile of PsA patients was characterized by a significant increase in glucose and glycyl proline, and a significant decrease in alanine, glutamine, methionine, serine and the branched-chain amino acids leucine, isoleucine and valine. The ROC curve was 0.842 (95% CI 0.735–0.949), and a significant direct correlation of alanine and leucine levels with the DAPSA score was recorded. Finally, the enrichment analysis unveiled that in PsA patients, the most enriched pathways were glucose-alanine cycle, glycine and serine, glutathione, selenoamino acid, alanine and tryptophan metabolism, with a close relationship between pathways. The metabolomic profiling in PsA may offer additional insight to elucidate the metabolite unbalance on inflammatory burden, oxidative stress, energy and collagen metabolism, but also on peculiar features of the disease, such as metabolic disorders and diabetes.

The online version contains supplementary material available at 10.1038/s41598-025-34101-4.

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