Rheumatoid arthritis

Time-resolved immune dynamics in rheumatoid arthritis under methotrexate therapy

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

Together, these findings reveal an unexpectedly rapid and coordinated immune reconfiguration after MTX initiation and position early alterations in Tfh cells and plasmablasts as biomarkers of treatment response.

Study context

Population
Newly diagnosed patients with rheumatoid arthritis (RA) initiating methotrexate (MTX)validation cohort of 22
Participants
6 participants
Outcome
Time-resolved immune changes under MTX
Methodological detailsprospective longitudinal, single-cell multiomics, independent validation cohort
  • Prospective longitudinal
  • Single-cell multiomics
  • Independent validation cohort

Main finding

As reported in the abstract

  • Rapid immune remodelling detectable as early as 3 weeks after MTX initiation, preceding clinical improvement
  • T follicular helper (Tfh) cells and plasmablasts declined selectively in clinical responders but remained largely unchanged in nonresponders across independent cohorts and external datasets
  • Functional plasmablast differentiation assays linked MTX treatment to impaired development
  • Regulatory hubs associated with MTX exposure: LMNA, SCO2, GVQW3, GIMAP family members

Original publication

Time-resolved immune dynamics in rheumatoid arthritis under methotrexate therapy. Ann Rheum Dis. Published 11 June 2026. doi:10.1016/j.ard.2026.05.018

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