Study: Inflammation Starts Earlier Than You Think

Each of these omic assays generates large datasets, so integration involves using computational algorithms and powerful computing platforms to bring together the disparate pieces of data to create a systemwide view of human immunity in the setting of disease. Tools to do this type of analysis at scale in humans have become available relatively recently, facilitating our ability to do systems immunology to generate a more complete picture of immune-mediated diseases, such as RA. Our hope is that this approach will yield new insights, as described in our paper, that will provide opportunities for early, targeted interventions.

Dr. Mark Gillespie

Dr. Gillespie: Multiomics approaches allow us to profile the various molecular features of a system in a mostly unbiased manner. For instance, to understand the state of a cell, which can provide clues as to its function, we can profile that cell’s transcriptome or proteome—the molecular changes occurring inside that cell. Making these measurements independently gives us one level of information, but processing and interpreting them together in an integrative manner provides deeper insights into the identity of this cell, what it may be doing, what other cells it may be communicating with and what might be going wrong in autoimmune diseases like RA.

By applying integrative multiomics approaches in rheumatology research, we can generate a more comprehen­sive, system-level view of the disease-relevant changes. These changes may represent critical drivers of disease pathology or important biomarkers of disease onset or progression—information that can provide the future basis for more personalized therapeutics and/or prevention strategies.

TR: What should practicing rheumatologists take away from these findings?

Dr. Deane: At a high-level, this study again demonstrated that ACPA-positive individuals are at high risk for developing clinical RA. While more work needs to be done, we plan in the near future to translate the findings from this study into actionable prediction models, and ultimately preventive interventions for RA, that can be used in the routine clinical care of individuals who are at risk for RA.

Importantly, while RA is one of the more common chronic autoimmune diseases, it’s still relatively rare because it only affects about 1% of the population. As such, people who are at risk for RA because of ACPA positivity are also relatively rare—although such individuals are seen in rheumatology clinics periodically.

To help the next generation of studies on the prediction and prevention of RA, we need networks of rheumatologists and people who are at risk for RA to participate in research studies. To help in this area, a new study that has evolved from this collaborative effort between the Allen Institute, University of California, San Diego and University of Colorado Anschutz is called StopRA: National. It offers opportunities for rheumatologists and people who are ACPA positive across the U.S. to participate remotely in a research study to learn more about how RA develops. More information about StopRA: National can be found at https://tinyurl.com/w8aaz45k.