Kathleen Hagerty Provost | Northwestern University
Symptoms that persist long after antibiotic treatment for Lyme disease are not uncommon, and a study conducted in 2022 revealed that 14% of those treated early for the disease still developed Post Treatment Lyme Disease (PTLD). Doctors remain puzzled by the causes of this condition, which presents symptoms ranging from severe fatigue to cognitive challenges and arthritis.
Northwestern University scientists propose that the persistence of symptoms could be due to a lingering response to remnants of the Borrelia burgdorferi cell wall. These remnants break down during treatment but may remain in the liver, spurring an exaggerated immune response. This theory aligns with one idea about the causes of long COVID-19, where residual viral molecules trigger unnecessary immune activity, according to bacteriologist Brandon L. Jutras.
“Lyme and long COVID-19 are clearly vastly different diseases, but it’s possible that they share a more general mechanism of inappropriate inflammation caused by remnants of a previous infection,” remarked Jutras, who led the research. “The maladaptive response is a product of an infection, but perhaps not necessarily an active one in all cases.”
The research, published in Science Translational Medicine, investigated the biodistribution of peptidoglycan, a bacterial cell wall component, and found that it sheds quickly except in Lyme disease, where the peptidoglycan persists for weeks or months. Jutras explained that Lyme arthritis, a common long-term effect, can cause synovial fluid in joints to contain the peptidoglycan long after treatment.
Jutras noted, “In the context of Lyme arthritis, if you give patients anti-inflammatory, disease-modifying antirheumatic drugs, they get better. Some of these very same patients do not get better after oral and IV antibiotics, which implies there is something unique about how patients respond at a genetic level.”
Jutras has been studying Lyme disease for over 15 years and is now an associate professor at Northwestern University’s Feinberg School of Medicine. He described peptidoglycan as a critical component making Lyme bacteria unique, affecting its persistence in the body.
“The unusual chemical properties of Borrelia peptidoglycan promote persistence, but it’s the individual patient response to the molecule that likely impacts the overall clinical outcome,” Jutras commented. He noted differing immune responses among patients could influence the severity of symptoms.
Jutras aims for these findings to lead to better diagnostic tests and treatments for PTLD, particularly for when antibiotics do not succeed. Efforts are focused on neutralizing inflammatory molecules rather than infection, including the use of monoclonal antibodies targeting peptidoglycan.
The research received funding from several organizations, including the National Institutes of Allergy and Infectious Diseases and the Global Lyme Alliance.