Dr. Cope also discussed what is being learned at the epigenetic level about patients who are at risk for RA. In looking at these patients, it appears that chromatin signatures associated with progression to RA map to loci associated with the CD28 co-stimulation pathway. Specifically, Dr. Cope showed that two areas on chromosome 1 implicated in this pathway are linked to the gene PTPN22, which for nearly 20 years has been of interest to understanding the genetic risk factors for autoimmunity. (In 2004, researchers reported that a single-nucleotide polymorphism C1858T [rs2476601] in the PTPN22 gene was associated with type 1 diabetes, RA and systemic lupus erythematosus) 3. By looking at epigenetic modifications—DNA methylation, histone modification, chromosome remodeling, RNA interference—that affect and regulate the function and characteristics of genes, we may be able to better understand why some patients who are at risk for RA progress to disease and others do not.
In Sum
All three speakers in the session provided valuable insights into a timely topic. In 2024, the goal is not just to treat patients with RA, but it is also to identify those at risk for the disease and, perhaps, prevent its onset altogether.
References
- van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJet al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):491-496.
- Cope AP, Jasenecova M, Vasconcelos JC, et al. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): A randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024 Mar 2;403(10429):838–849. 3.
- Mustelin T, Bottini N, Stanford SM. The contribution of PTPN22 to rheumatic disease. Arthritis Rheumatol. 2019 Apr;71(4):486-495.
Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.
