New Study Sheds Light on the Biology Behind Lyme-Related Arthritis

A new study led by Brandon L. Jutras, Ph.D., associate professor at Northwestern University Feinberg School of Medicine, funded in part by Bay Area Lyme Foundation, offers new insight into why some people develop severe, long-lasting arthritis after Lyme disease, even after receiving appropriate antibiotic treatment, while others recover fully.

Lyme disease occurs when a tick carrying the bacterium Borrelia burgdorferi feeds long enough to transmit the infection. In many cases, antibiotics successfully kill the bacteria. However, Jutras explains that when antibiotics destroy Borrelia, they also expose internal bacterial components. One of these components, called peptidoglycan, is a structural molecule that forms the bacterium’s cell wall. This molecule is highly inflammatory and, importantly, appears to persist in the body long after the infection itself has been cleared.

The persistence of peptidoglycan may help explain why inflammation continues in some patients. While inflammation is normally a helpful immune response that aids infection clearance, uncontrolled or prolonged inflammation can lead to complications such as arthritis. According to Jutras, not all patients respond to this lingering molecule in the same way. The research team believes genetic differences in the immune system (specifically variations in proteins that recognize bacterial components) may cause certain individuals to mount an exaggerated and long-lasting inflammatory response. In others, the same molecule may be largely harmless.

To explore this theory, the team of investigators made subtle changes to the chemical structure of Borrelia’s peptidoglycan in a preclinical animal model. Surprisingly, these changes did not prevent the bacteria from infecting and spreading through the body. However, they nearly eliminated the development of arthritis. This finding suggests that specific structural features of the bacterial cell wall, not ongoing infection, are key drivers of Lyme-related arthritis.

The study also opens the door to potential new treatment approaches. Jutras describes strategies that focus on neutralizing or removing lingering peptidoglycan rather than targeting the bacteria itself. One approach involves using monoclonal antibodies to “mask” the inflammatory molecule so the immune system no longer reacts to it. Another strategy would tag the molecule for destruction by the immune system.

While these ideas are still in early, preclinical stages, Jutras encourages cautious optimism. The research provides a clear biological target for future therapies, particularly for patients whose symptoms persist after standard treatment. However, more studies, funding and regulatory steps are needed before these approaches can be tested in people. The work also aligns with broader efforts to understand postinfectious conditions, including parallels with long COVID.