THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14


Molecular-level advances lead to improved understanding of vasculitis

Peter Grayson, MD, MSc
Peter Grayson, MD, MSc

New technologies make it possible to measure tens of thousands of cells at once, giving researchers an opportunity for improving our understanding of disease on a molecular level. 


Two such investigators will bring attendees up to date on the latest in this area of research during a the Tuesday Basic Science session Epigenetics & Transcriptomics of Vasculitis: Insights on Pathogenesis, which will take place from 1:00 – 2:00 pm in Room B309, Building B in the Georgia World Congress Center.


Peter Grayson, MD, MSc, head of the Vasculitis Translational Research Program at the National Institutes of Arthritis and Musculoskeletal and Skin Diseases, will focus his remarks on the transcriptomics of ANCA-associated vasculitis.


“This session is really about translational research in vasculitis,” he said. “There are approximately 30,000 genes expressed by a cell, and now, with transcriptomic technology, we can measure all of them simultaneously. In the past, we had to look at a specific gene. Now we can look at genes in a much more hypothesis-naïve way.”


The hope is that researchers can potentially characterize these diseases on a molecular level. 


“That’s the theory,” Dr. Grayson said. “Then there’s the practicality of how much we’ve learned with these approaches. What are the successes? What are the failures? How can we harness this technology effectively to ask clinical questions? What are the pressing needs clinically in these conditions? How can we leverage this technology to begin to address those needs.”


Dr. Grayson will review what is known about the answers to those questions regarding ANCA-associated vasculitis during his talk.


“For ANCA vasculitis, we’re in a really nice space clinically because there are a lot of effective treatments,” he said. “We also have good, evidence-based data for how to use those treatments. But most of those treatments are focused on getting the disease to go into remission. The challenging part of this disease is that it often relapses and comes back unpredictably. So we can keep people on expensive medications with potential side effects for indefinite periods of time. Or we can try to get smarter at figuring out who needs these medications and for how long. That’s where I think genomic studies may help us at a clinical level. Trying to discover biomarkers that will predict clinical outcomes and guide treatment decisions is a major unmet need in vasculitis.”


Dr. Grayson said researchers looking at every rheumatic disease face the same struggle. 


“Can we profile patients deeply at the molecular level and use that to determine what treatment they may need upfront?” he asked. “Can you profile them when they’re doing well to determine when it’s time to come off treatment? Can you profile them to help you with long-term prognosis?”


Dominic Ciavatta, PhD
Dominic Ciavatta, PhD

Fellow presenter Dominic Ciavatta, PhD, Associate Professor of Genetics at the University of North Carolina, Chapel Hill, concurred. 


Dr. Ciavatta, who will talk about the epigenetics of vasculitis, said this research is important because many current therapies for rheumatologic and immunologic diseases are general immunosuppressants. He said improving the understanding of specific mechanisms that are occurring in these diseases could lead to more targeted therapies. 


“One area that we’ve focused on is the actual target of the autoantibodies,” Dr. Ciavatta said. “Those of us researching ANCA-associated vasculitis are fortunate because we know those targets. Our work could become a kind of a model for other disease researchers. If you can identify the targets within the disease, the results I’m going to present may be a road map for other researchers to follow.” 


He will share information from his work looking at how the targets of the autoantibodies are transcriptionally regulated. 


“We’ve looked at some signatures of the chromatin that can regulate the process that turns the autoantigens on and off,” Dr. Ciavatta said. “So we’ve identified a signature of modifications that are associated with disease activity.”


Dr. Ciavatta’s group has looked at patients over a long period of time, so they could study them when they have active disease and when they’re in remission.


“We found that a change in that modification was predictive of the probability of a relapse,” he said. “So the idea is that, in conjunction with other markers, you’d have a signature that can tell if a patient is in a long-term remission or likely to relapse. The next question is how do we control that modification.”