Transiently increased circulating CD39⁺FoxP3⁺ Treg cells predicts the clinical response to methotrexate in early rheumatoid arthritis.

This article focuses on the role of circulating CD39-expressing FoxP3⁺ regulatory T cells (cTreg39⁺) in early rheumatoid arthritis (eRA) and their interaction with methotrexate (MTX) treatment. The study found that untreated eRA patients exhibit elevated frequencies of cTreg39⁺ cells compared to healthy controls, and higher baseline levels of these cells predict better clinical response to MTX after 12 months, independent of other clinical factors. In vitro experiments demonstrated that MTX enhances the suppressive potency of cTreg39⁺ cells via the adenosine pathway, an effect blocked by inhibitors of CD39 or adenosine receptor A2A. Additionally, the initially elevated cTreg39⁺ cell frequency decreases following MTX treatment but remains associated with disease activity control. These findings suggest that cTreg39⁺ cells may serve as a biomarker for MTX responsiveness and highlight a potential therapeutic window for early intervention in eRA.