Investigators from HSS and collaborating centers identified distinct immune cell patterns in blood that signal an increased risk of developing rheumatoid arthritis (RA) before symptoms occur. The discovery represents a key milestone in creating a blood test that could help doctors identify patients at higher risk of the disease.
The study, presented today at the annual meeting of the American College of Rheumatology, ACR Convergence 2024, was led by researchers at the University of Colorado School of Medicine in collaboration with investigators from HSS and other centers within the Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network.
“These research findings validate the importance of certain immune cells in the development of RA, particularly in how they drive the change from asymptomatic to symptomatic,” said Laura Donlin, PhD, scientist and co-director of the HSS Precision Medicine Program and co-principal investigator of the National Institutes of Health-supported AMP Rheumatoid Arthritis research consortium. “We hope that one day we can use these insights to stop RA before it even begins.”
Rheumatoid arthritis is a type of inflammatory arthritis that can occur when specific types of immune cells attack the body’s healthy tissues, resulting in pain, swelling and stiffness in joints. It can also result in problems in other areas of the body, such as the heart, lungs, eyes, nerves and skin. Diagnosis typically relies on an evaluation by a rheumatologist for clinical signs and symptoms supported by further evidence from X-rays and blood tests.
For the study, the participating rheumatologists collected tissue and blood samples from patients who either had RA or were considered at risk due to specific antibodies, called ACPA, in their blood and having a first-degree relative with the disease. Researchers at the Broad Institute of MIT and Harvard then used advanced single-cell sequencing techniques to analyze the samples and compared the results to those from healthy individuals.
The analysis found higher numbers of certain immune cells in the patients at risk for RA, including CCR2+ T helper cells, T peripheral helper cells, type 1 T helper cells, and granzyme B-positive memory T helper cells. Advanced sequencing also gave the investigators a better understanding of which genes were activated in these cells, offering insight into how the immune cells in patients with RA differ from those in at-risk individuals and healthy people.
“We knew that the presence of ACPA in blood and having a first-degree relative with rheumatoid arthritis indicate risk, but this new research has allowed us to learn more about the underlying biology driving increased risk,” said HSS rheumatologist Susan M. Goodman, MD, a co-author of the study. “These insights will pave the way toward helping us develop a new tool for determining which patients may benefit from early intervention.”
“There is some evidence that existing RA drugs, such as abatacept or rituximab, may help prevent the disease, but they are relatively expensive and come with side effects,” said co-author S. Louis Bridges, Jr., MD, PhD, physician-in-chief and chief of the Division of Rheumatology at HSS. “Pending validation in larger studies, the new patterns of immune cells identified in this research could represent potential targets for the development of new, more effective therapies.”
