Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action

Background: Methotrexate (MTX) is the fi rst line treatment of rheumatoid arthritis (RA),
and methylation changes in bulk T cells have been reported after treatment with MTX. We
have investigated cell-type speci fi c DNA methylation changes across the genome in naïve
and memory CD4
T cells before and after MTX treatment of RA patients. DNA
methylation pro fi les of newly diagnosed RA patients (N=9) were assessed by reduced
representation bisul fi te sequencing.
Results: We found that MTX treatment signi fi cantly in fl uenced DNA methylation levels at
multiple CpG sites in both cell populations. Interestingly, we identi fi ed differentially
methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to
predict treatment outcome in RA patients when measured in bulk T cells. Furthermore,
several of the genes, including STAT3, annotated to the signi fi cant CpG sites are relevant
for RA susceptibility or the action of MTX.
Conclusion: We detected CpG sites that were associated with MTX treatment in CD4
naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic
regions previously associated with RA risk and MTX treatment outcome.


Use and reproduction:

CC BY 4.0

Please note that individual components of the publication may be subject to other licensing or copyright conditions.


Citation style:
Could not load citation form.