Understanding of inflammatory subtypes in RA may lead to more personalized treatment
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Key takeaways:
- Technological advances have enabled research into inflammatory subtypes.
- Defining inflammatory subtypes in rheumatoid arthritis may lead to tailored treatments for patients.
The mission to understand rheumatoid arthritis inflammation at a molecular level has gained momentum with the rapid evolution of cutting-edge technologies, allowing researchers to delve deeper into the individual differences in inflammatory subtypes.
In an exclusive Healio interview, Anna Helena Jonsson, MD, PhD, assistant professor of medicine-rheumatology at University of Colorado Anshutz Medical Campus, shared insights into research she has co-authored that could lead to a revolution in RA care. In the recent study, published in Nature, Jonsson and her co-authors sought to define the different subtypes of inflammation that can occur in the joints of RA patients.
“I feel lucky as a rheumatologist to have many tools in my toolbox, but I still don't have any way to know which tool is going to help this patient the fastest. So we have to use sort of a guess and check method,” Jonsson explained, underscoring the ongoing challenge of tailoring treatments to individual patients.
"Not all rheumatoid arthritis patients respond to the same treatments,” Jonsson said. The recent research into inflammatory subtypes may be a step in a direction that could lead to more personalized treatment.
Understanding Inflammation at the Molecular Level
Jonsson and colleagues’ study, a collaborative effort involving academic medical centers, the NIH and various pharmaceutical companies, may change how rheumatologists evaluate patients in the quest to provide more personalized treatment.
Researchers analyzed samples of synovium, specialized cells that lubricate and cushion the joints, but are inflamed in patients with RA, taken from 79 patients diagnosed with RA. They employed single-cell RNA sequencing and incorporated surface protein data alongside tissue samples to construct a comprehensive single-cell atlas of RA synovial tissue.
As a result, researchers identified six major types of inflammation that they grouped into phenotype-based categories. The six categories, known as cell-type abundance phenotypes (CTAPs), include endothelial, fibroblast and myeloid cells, fibroblasts, T cells and fibroblasts, T and B cells, T and myeloid cells, and myeloid cells.
“We're hoping that defining these different kinds of inflammation will help us match patients with treatments, either patients with treatments that are available now or patients with the need for new treatment targets,” Jonsson said.
The heterogeneity among patients with RA poses a significant challenge in determining effective treatment strategies, Jonsson said.
“There’s no way for me as a rheumatologist to identify when someone walks in through the door if they're going to be the kind of person that responds to a TNF inhibitor or an IL-6 blocker or a B-cell depleting agent,” Jonsson said.
Jonsson hopes that this recent research signifies a pivotal moment in reshaping how rheumatoid arthritis is approached and treated.
The Need for Advanced Technologies
The rapid pace of technological advancements in recent years, particularly in the realm of human translational studies, has paved the way for this research, Jonsson said.
With human patient samples, such as synovial tissue from patients with rheumatoid arthritis, the challenge lies in the minuscule size of these tissues.
“When it comes to human patient samples, the pieces of tissue that we can get from, for example, synovial tissue, like joint capsule tissue from patients with rheumatoid arthritis, they're teeny, tiny,” Jonsson said.
Traditionally, obtaining meaningful information from these small samples has been difficult and limited.
“Contributing synovial tissue to research is such a generous thing for patients to do, so it was frustrating to only be able to get a tiny bit of information from each sample,” she said.
However, recent innovations, including single-cell RNA sequencing and advances in SITE-seq technology, have transformed the landscape, Jonsson said.
These technologies now enable researchers to extract vast amounts of information from even the smallest tissue samples, offering a more comprehensive understanding of the molecular intricacies of RA. In this study, researchers evaluated more than 314,000 cells from samples of synovial tissues.
Defining Subtypes of Inflammation
The collaborative effort of this study and recent technological advancements are not only unraveling the mysteries of RA but also opening new avenues for treatment innovation.
By defining distinct subtypes of inflammation, rheumatologists hope to tailor treatments more precisely to individual patients. This could revolutionize the field, providing a more targeted and effective approach to managing rheumatoid arthritis, Jonsson said.
The ongoing research underscores the transformative potential of molecular insights and collaborative endeavors in the realm of rheumatoid arthritis. With each technological leap, the path to personalized medicine becomes clearer, Jonsson emphasized, providing renewed hope for a future where the mysteries of RA are not only unraveled but also effectively addressed, improving the lives of those affected by this complex autoimmune condition.
“What we need next are more studies that include synovial tissue when they’re studying the responses to different treatments, either treatments that already exist or new treatments, so we can start to flesh out this picture of how these different categories of RA respond to given treatments that are available,” Jonsson said.
References
- Zhang, F., Jonsson, A.H., Nathan, A. et al. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature 623, 616–624 (2023)
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