- Gary Firestein, MD, distinguished professor of medicine, University of California, San Diego;
- Kevin Deane, MD, professor, medicine-rheumatology, University of Colorado Anschutz, Aurora;
- Troy Torgerson, MD, PhD, director, experimental immunology, Allen Institute for Immunology, Seattle; and
- Mark Gillespie, PhD, assistant investigator, Allen Institute for Immunology, Seattle.
Interview
The Rheumatologist (TR): How would you summarize your findings?
Dr. Kevin Deane
Dr. Deane: Prior studies have demonstrated that individuals who have elevated blood levels of ACPAs are at high risk for the future development of full-blown RA, which can also be called clinical RA. However, not all ACPA-positive, at-risk individuals get clinical RA. In addition, the biology that drives a transition from an at-risk state to clinical RA isn’t fully understood.
With this study, we evaluated ACPA-positive individuals, a portion of whom developed clinical RA during the approximately seven years of the study. We were able to deeply evaluate the immune system across time as these at-risk individuals ‘converted’ to clinical RA. The key findings were that there are multiple immune system abnormalities in T and B cells, as well as systemic inflammation, even prior to the onset of clinical RA.
Going forward, we plan to build on these findings to develop improved ways to predict future RA and target specific biologic processes to improve our current therapies for RA, as well as to ultimately prevent RA.
Dr. Gary Firestein
Dr. Firestein: Clinicians often encounter patients with family histories of RA or an isolated positive test, like anti-cyclic citrullinated protein (anti-CCP) antibody. Currently, there is little guidance on how to proceed beyond watchful waiting.
Our study provides a road map for the immunological changes that occur as someone moves from asymptomatic autoimmunity to RA. As we continue to dissect these pathways, newer tests will hopefully be available that will help determine who has the greatest risk of progression and perhaps even the best ways to prevent RA.
TR: Integrative multiomics is likely a new concept to most of our readers. How is this technology changing the rheumatology research landscape?
Dr. Troy Torgerson
Dr. Torgerson: Multiomics describes an approach of utilizing a variety of omic assays (transcript-omics, prote-omics, etc.) to broadly, deeply and simultaneously measure many aspects of a biological system. Integrative means trying to correlate the biology observed in one ome with that observed in a second, third or fourth ome.
