DNA Methylation at Diagnosis is Associated with Response to Disease-Modifying Drugs in Early Rheumatoid Arthritis

Abstract

Aim: A proof-of-concept study to explore whether DNA methylation at first diagnosis is associated with response to disease-modifying antirheumatic drugs (DMARDs) in patients with early rheumatoid arthritis (RA). Patients & methods: DNA methylation was quantified in T-lymphocytes from 46 treatment-naive patients using HumanMethylation450 BeadChips. Treatment response was determined in 6 months using the European League Against Rheumatism (EULAR) response criteria. Results: Initial filtering identified 21 cytosine-phosphate-guanines (CpGs) that were differentially methylated between responders and nonresponders. After conservative adjustment for multiple testing, six sites remained statistically significant, of which four showed high sensitivity and/or specificity (≥75%) for response to treatment. Moreover, methylation at two sites in combination was the strongest factor associated with response (80.0% sensitivity, 90.9% specificity, AUC 0.85). Conclusion: DNA methylation at diagnosis is associated with disease-modifying antirheumatic drug treatment response in early RA.

Keywords::

• disease activity score with 28 joint counts (DAS28)
• disease-modifying antirheumatic drugs (DMARDs)
• DNA methylation
• early rheumatoid arthritis
• Illumina 450K array
• T-lymphocyte
• treatment response

Acknowledgements

The authors would like to thank the patients who participated in the study. They also thank J Turner, C Thwaites and M Dishman for assistance with the collection of clinical data.

Financial & competing interests disclosure

This work was supported by funding from the Haywood Rheumatism Research and Development Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by funding from the Haywood Rheumatism Research and Development Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.