Association of Epigenetic Trajectory With Development of Clinical Rheumatoid Arthritis in Individuals With Anti–Citrullinated Protein Antibody Positivity: Targeting Immune Responses for Prevention of Rheumatoid Arthritis ( TIP ‐ Rheumatoid Arthritis (RA) )
Authors' conclusion
DNA methylation is a dynamic process that continuously remodels in individuals who were asymptomatic and anti-CCP3 positive as they progress to disease, whereas it remained relatively stable in nonconverters and controls.
Study context
- Population
- ACPA-positive individuals without clinical inflammatory arthritis at risk for RA, anti-CCP3-negative controls and patients with early RA
- Exposure
- ACPA-positive converters vs nonconverters vs anti-CCP3-negative controls vs early RA
- Outcome
- Differentially methylated loci (genome-wide DNA methylation in CD4 T memory, naive and B cells) distinguishing converters from nonconverters
Methodological detailsgenome-wide DNA methylation, longitudinal sampling up to five years, machine-learning prediction
- Genome-wide DNA methylation
- Longitudinal sampling up to five years
- Machine-learning prediction
Main finding
As reported in the abstract
DNA methylation (DMLs) by group
- At baseline, DMLs clearly separated converters from nonconverters and patients with early RA
- Enrichment of aberrant NOTCH signaling and DNA repair pathways particularly prominent in B cells
- Methylomes stable in controls and nonconverters but progressively remodelled in converters, tracing an "RA methylome trajectory" toward the early RA methylome
- Machine-learning models incorporating top CpG predictors accurately classified future converters with RA
Observational data: associations, not effects.
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Association of Epigenetic Trajectory With Development of Clinical Rheumatoid Arthritis in Individuals With Anti–Citrullinated Protein Antibody Positivity: Targeting Immune Responses for Prevention of Rheumatoid Arthritis ( TIP ‐ RA ). Arthritis Rheumatol. Published 22 April 2026. doi:10.
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