Research from the Yale School of Medicine has identified a significant mechanism responsible for ongoing joint destruction in individuals with rheumatoid arthritis (RA), despite treatment advancements. The study, published in the Proceedings of the National Academy of Sciences, highlights the role of specific immune cells in the persistence of joint damage associated with this autoimmune disease, which affects approximately 1.5 million Americans and nearly 5% of women over the age of 55.
The research team, led by Edward Doherty, PhD, along with collaborators Lais Osmani, MD, MHS, and Joshua Bilsborrow, MD, MHS, focused on the function of T lymphocytes, a type of white blood cell, in mouse models of arthritis. Their findings reveal that a subset of these cells possesses a receptor for the immune hormone known as macrophage migration inhibitory factor (MIF). Previous studies have indicated that many individuals with autoimmune conditions exhibit overactivity of the MIF gene, which correlates with more severe disease manifestations.
The research demonstrated that these MIF-sensitive T lymphocytes are expanded in models of joint inflammation. Remarkably, transferring these cells to healthy mice resulted in RA-like joint inflammation, suggesting a direct link between these lymphocytes and disease progression. Moreover, researchers identified these cells in joint tissues from RA patients requiring joint replacement surgery.
According to Richard Bucala, MD, PhD, the Waldemar Von Zedtwitz Professor of Medicine (Rheumatology), these T lymphocytes function similarly to memory cells. This means they retain their autoimmune characteristics long after the initial inflammatory response has subsided, whether through natural resolution or medical intervention. Bucala notes that during RA relapses, inflammation typically re-emerges in joints previously affected, which may be attributable to the persistence of these memory T lymphocytes.
The implications of this research are significant. The findings suggest that the ongoing presence of these cells contributes to gradual joint destruction in many patients who may feel well while on therapy. Bucala emphasizes that even patients receiving the most effective treatments can have underlying inflammation that continues to damage their joints over time.
The progress made in biologic therapies over the past 25 years has diminished the urgency for a cure for RA, yet it has increased the necessity for strategies that address the underlying mechanisms of the disease. Bucala asserts that understanding these memory T cells is crucial for developing new therapeutic approaches.
Other contributors to the study from Yale include Jennefer Par-Young, Marta Piecychna, Lin Leng, and Insoo Kang. The Rheumatology, Allergy and Immunology section of the Yale Department of Internal Medicine is dedicated to patient care, education, and research in the fields of rheumatic, allergic, and immunologic disorders. For further information, visit the Yale Department of Internal Medicine’s website.
