# Dual Specificity Phosphatase (DUSP22) promoter hypomethylation in cell-free DNA is associated with rheumatoid arthritis and its radiographic severity

## TL;DR

This study finds that lower DNA methylation in the DUSP22 gene in cell-free DNA is linked to rheumatoid arthritis and more severe joint damage, suggesting a potential non-invasive biomarker.

## Contribution

This is the first study to explore cfDNA DUSP22 methylation as a potential biomarker for rheumatoid arthritis and its severity.

## Key findings

- RA patients had lower DUSP22 DNA methylation in cfDNA compared to healthy controls.
- Lower DUSP22 methylation was associated with increased joint space narrowing in RA patients.
- Age was significantly correlated with decreased DUSP22 DNA methylation in RA patients.

## Abstract

While several advances have been made in the last decade, reliable biomarkers for disease activity, prognosis, and response to treatment of rheumatoid arthritis (RA) have yet to be identified. In previous studies, DUSP22 DNA methylation changes were found to be associated with RA and erosive disease. We conducted a pilot study to investigate plasma cell-free DNA (cfDNA) methylation in DUSP22 in a cohort of RA patients and healthy controls. We also investigate DUSP22 DNA methylation associations with RA clinical characteristics and treatment.

DNA was isolated from plasma from 27 RA patients who satisfied the ACR criteria, and 18 healthy controls. DUSP22 DNA methylation was determined by pyrosequencing. Statistical analysis identified group differences and associations with RA clinical measures.

RA patients had lower cfDNA DUSP22 DNA methylation at one specific DNA methylation site in the promoter region when compared to controls (36.7 ± 3.3% for RA versus 46.9 ± 2.6% for controls, age-adjusted-p = 0.049). For RA patients, age was associated with a significant decrease in DUSP22 DNA methylation for all sites and the promoter region (βmean = −0.64, p = 0.02). Lower DNA methylation was also associated with increased joint space narrowing (ρCpGMean = −0.40, p = 0.05).

Our pilot study is the first to evaluate cfDNA methylation association to RA clinical characteristics. These exploratory findings suggest that DUSP22 cfDNA methylation may represent a promising non-invasive biomarker in rheumatoid arthritis, a hypothesis that warrants validation in larger and ethnically diverse populations.