Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in...

Area of Science:

• Immunology
• Epigenetics
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease.
• Methotrexate (MTX) is a common treatment for RA, but response varies significantly among patients.
• Understanding the molecular mechanisms underlying MTX response is crucial for personalized treatment strategies.

Purpose of the Study:

• To investigate cell-specific DNA methylation (DNAm) changes associated with MTX treatment response in RA patients.
• To identify potential epigenetic biomarkers for predicting MTX efficacy.

Main Methods:

• Whole blood samples were collected from RA patients (n=77) at baseline and after MTX treatment.
• DNA methylation profiles were analyzed using Illumina MethylationEPIC arrays.
• Cell-specific differential DNAm was identified using Tensor Composition Analysis.
• MTX response was determined by EULAR criteria.

Main Results:

• Cell-specific differential DNA methylation patterns were associated with MTX treatment response.
• One differentially methylated position was identified in CD4+ T cells, CD8+ T cells, and natural killer cells at baseline.
• Thirty-nine cell-specific differentially methylated regions were linked to MTX response.
• No significant findings were observed in bulk whole blood analyses.

Conclusions:

• Cell-specific DNA methylation changes are associated with MTX treatment response in RA.
• Future studies should focus on DNAm analysis in sorted immune cells for better insights into MTX response.
• This research may pave the way for novel epigenetic biomarkers in RA treatment.