Published Nov. 29, 2016
Proceedings of the National Academy of Sciences
Anti-TNF therapy has helped many people with juvenile idiopathic arthritis (JIA) achieve remission. However, up to 80 percent of patients flare upon treatment withdrawal, thus requiring continued exposure to the risks and costs of an immunosuppressive biologic.
Now, a multi-center research team reports that measuring the genome-wide DNA methylation status of circulating CD4+ T cells reveals biological changes occurring in JIA patients that can predict which patients are at the highest risk of relapse upon treatment withdrawal.
The team included senior co-author Daniel Lovell, MD, MPH, Division of Rheumatology, who serves as chairman of the national Pediatric Rheumatology Collaborative Study Group. Lovell was the principal investigator on a 16-center clinical trial that enrolled the patients, collected biospecimens, and provided other key data used in this study.
Scientists have known that JIA reflects a complex interplay between genetics and environment. This study explored the epigenetic changes occurring in a cohort of 68 JIA patients, using samples of T cells collected upon treatment withdrawal and at the time of disease flare-up.
“We observed clear differences in DNA methylation of immunologically relevant genes—particularly those involved in T-cell activation and TCR signaling—in patients with divergent clinical outcomes, which were not associated with age or gender,” the authors state. “To our knowledge, our work is unique in proposing an epigenetic discrimination between clinical activity states.”
The study suggests potential for DNA methylation as a tool for identifying predictive biomarkers of disease activity.
“If borne out in validation studies, then this test has the possibility to be developed into a predictive test to inform treatment of children with JIA who have demonstrated excellent response to treatment, which ones need to be continued on therapy, and which can be effectively taken off treatment,” Lovell says.