# Metabolomics in juvenile idiopathic arthritis: A distinct profile in patients under methotrexate

**Authors:** Renato B. Tomioka, Gabriela R.V. Ferreira, Nadia E. Aikawa, Gustavo A.R. Maciel, José M. Soares Junior, Edmund C. Baracat, Eloisa Bonfá, Ismael Dale Cotrim Guerreiro da Silva, Clovis Almeida da Silva

PMC · DOI: 10.1016/j.clinsp.2024.100522 · Clinics · 2025-01-28

## TL;DR

The study found a unique metabolic pattern in children with juvenile idiopathic arthritis who are taking methotrexate, suggesting better mitochondrial function.

## Contribution

The study identifies a distinct serum metabolic profile in JIA patients on methotrexate therapy.

## Key findings

- Methotrexate use is associated with increased free carnitine levels and improved mitochondrial function.
- Polyarticular and systemic JIA subtypes show decreased mitochondrial metabolism and acylcarnitine concentrations.
- Metabolomic analysis revealed distinct serum metabolic signatures in JIA patients under methotrexate therapy.

## Abstract

•We identified a distinctive pattern of serum metabolic signatures in juvenile idiopathic arthritis patients under methotrexate therapy.•Methotrexate use is associated with a more efficient mitochondrial function.•A decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines’ concentrations.

We identified a distinctive pattern of serum metabolic signatures in juvenile idiopathic arthritis patients under methotrexate therapy.

Methotrexate use is associated with a more efficient mitochondrial function.

A decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines’ concentrations.

The objective of the present study was to evaluate biochemical quantitative metabolites in peripheral blood serum samples of Juvenile Idiopathic Arthritis (JIA) patients and healthy controls. A cross-sectional study included 33 post-pubertal JIA (21 without and 12 with Methotrexate (MTX) women and 28 age-matched healthy controls. Metabolomic analyses based on targeted electrospray ionization tandem mass spectrometry were used to identify possible biochemical pathway modifications in serum from JIA patients. The mean current age (p = 0.065) was similar in JIA patients and healthy controls. Current MTX use in all subtypes of JIA patients was associated with an increase in concentrations of free carnitine [21.74 (12.7‒35.2) vs. 27.49 (14.5‒41.3) µM/L, p = 0.02], suggesting an enhanced mitochondrial metabolism and intestinal absorptive function. In contrast, a decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines’ concentrations (p < 0.05). In conclusion, the present study identified a distinctive pattern of serum metabolic signatures in JIA patients under MTX therapy. Our findings indicate that MTX use is associated with a more efficient mitochondrial function.

## Linked entities

- **Chemicals:** methotrexate (PubChem CID 4112)
- **Diseases:** juvenile idiopathic arthritis (MONDO:0011429), polyarticular JIA (MONDO:0018456)

## Full-text entities

- **Diseases:** JIA (MESH:D001171)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11814531/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC11814531/full.md

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Source: https://tomesphere.com/paper/PMC11814531