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The following is a summary of “Red blood cell metabolomics identify ergothioneine as a key metabolite in DMARD-naïve rheumatoid arthritis and response to methotrexate,” published in the September 2024 issue of Rheumatology by Sigaux et al.

Metabolomic analysis on red blood cells (RBCs) with methotrexate (MTX) used in patients with rheumatoid arthritis (RA).

Researchers conducted a retrospective study to compare RBC metabolic profiles of patients with methotrexate-naïve rheumatoid arthritis to HCs and to investigate whether these profiles vary between responders and non-responders to methotrexate treatment.

They extracted metabolites from RBCs and plasma of 31 patients with Disease-Modifying antirheumatic drugs (DMARD-naïve) RA and 39 HCs. Further, they evaluated 25 patients with RA undergoing MTX treatment pre-treatment (M0) and after 3 months of treatment (M3). They analyzed metabolomic profiles using liquid chromatography-mass spectrometry (LC-MS) and compared metabolomic fingerprints using Storey’s false discovery rate (FDR) q-values to correct for multiple testing.

The results showed RBCs from patients with RA had increased levels of 4 carbohydrates, 2 amino acids (creatine, valine), and other metabolites, while citrulline (fold change = 0.83; q = 0.025), histidine (fold change = 0.86; q = 0.014), and ergothioneine (EGT) (fold change = 0.66; q = 0.024) were lower. In plasma, elevated succinic acid, hydroxyproline, and other metabolites, and reduced DHEA sulfate, alanine, threonine, ornithine, and other metabolites were observed among patients with RA and had lower EGT levels in nonresponders undergoing MTX treatment pre-treatment (M0).

They concluded low RBC levels of EGT, a food-derived amino acid barely detectable in plasma, characterized in patients with methotrexate-naive rheumatoid arthritis and lack of response to methotrexate treatment.

Source: nature.com/articles/s41598-024-68477-6