Novel DNA methylome biomarkers associated with adalimumab response in rheumatoid arthritis patients

Area of Science:

• Epigenetics
• Immunology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) treatment often involves cytokine blockade, like anti-tumor necrosis factor-alpha (TNFα) agents.
• Predicting patient response to biologic therapies, such as adalimumab (ADA), remains a clinical challenge.
• Biomarkers are needed to guide personalized treatment strategies for RA patients.

Purpose of the Study:

• To investigate DNA methylation patterns in peripheral blood leukocytes (PBL) as potential biomarkers for predicting ADA treatment response in RA patients.
• To develop a machine learning model using DNA methylation data to differentiate between responders and non-responders to ADA therapy.

Main Methods:

• DNA methylation profiling was performed on PBL from 92 RA patients prior to ADA treatment using the Illumina HumanMethylationEPIC BeadChip array.
• Treatment response was assessed after 6 months using European Alliance of Associations for Rheumatology (EULAR) criteria.
• Stability-selected gradient boosting models were employed to identify predictive DNA methylation markers (CpGs).

Main Results:

• A panel of 27 CpGs achieved high performance (AUC 0.76) in distinguishing ADA responders from non-responders.
• The identified CpGs are associated with genes involved in key RA-related pathways, including T-cell signaling, B-cell pathology, and angiogenesis.
• The study successfully classified 49 responders and 43 non-responders among 94 RA patients.

Conclusions:

• The DNA methylome of PBL possesses discriminative power for predicting ADA treatment response in RA.
• Epigenetic profiling of PBL could serve as a valuable tool for personalizing biologic therapy selection in rheumatoid arthritis.
• This approach may improve treatment efficacy and patient outcomes by enabling pre-treatment prediction of response.