By Clinical Research News Staff 

November 19, 2025 | Rheumatoid arthritis (RA) has a reputation as a lifelong condition with no real cure and can only be managed after symptoms appear. However, researchers from the Allen Institute for Immunology, University of California (UC), San Diego, and the University of Colorado Anschutz, have mapped out a way to detect dramatic immune system changes before the joints start swelling.  

Through a seven-year study, published in Science Translational Medicine (DOI: 10.1126/scitranslmed.adt7214), the research team tracked individuals who tested positive on an anti-citrullinated protein antibodies (ACPA) test using transcriptome and proteome profiling as well as immune cell phenotyping. Participants who developed the RA were shown to have an overactive immune system very early on before the disease was apparent and could be diagnosed, said Mark Gillespie, Ph.D., assistant investigator at the Allen Institute in Seattle and a senior author on the study.  

However, only one-third of ACPA-positive patients go on to develop RA, which means that two-thirds of enrollees never get the disease. As such, having more accurate predictive methods that identify those at the highest risk of progressing to clinical RA would result in shorter studies with fewer participants, explained Gary Firestein, M.D., senior associate vice chancellor for health sciences at UC San Diego. 

The findings are already reshaping the design of RA clinical research. Kevin Deane, M.D., Ph.D., professor of medicine at the University of Colorado Anschutz. and lead author of the StopRA prevention study (Arthritis & Rheumatology, DOI: 10.1002/art.43366) said this new knowledge “will help inform the next round of clinical trials.” The StopRA phase 2 trial, which tested hydroxychloroquine in ACPA-positive individuals, found the drug ineffective at preventing disease—underscoring the need for new, targeted interventions based on molecular insights. 

Future trials may soon stratify participants by immune cell signatures and communication networks rather than relying on elevated levels of anti-cyclic citrullinated peptide antibodies. That cellular “map” could guide both precision prevention and more personalized treatment strategies for those already diagnosed. 

With six prevention trials completed globally and more on the horizon, researchers believe RA is on the cusp of a paradigm shift. “This was not the end of the story ... [but] the beginning,” Firestein emphasizes. “We’re now at the point where we can see the roads, we can identify the intersections and know, hopefully, where they’re taking people.” 

To read the full story written by Deborah Borfitz, visit Diagnostics World News.