Further insights into persistent joint pain in Lyme disease

Recent research has revealed that better treatment for Lyme arthritis could be possible. Researchers found that the solution to the puzzle could lie in the cell walls of the bacteria responsible for the disease.

Immunizing peptidoglycan fragments could play a key role

Recent research has revealed that better treatment for Lyme arthritis could be possible. Researchers found that the solution to the puzzle could lie in the cell walls of the bacteria responsible for the disease.

According to the US-based Centers for Disease Control and Prevention (CDC), the number of Lyme disease cases has tripled since the 1990s. There is also a general trend toward tick-borne diseases. This is partly due to climate change and rising temperatures worldwide.

To combat the long-term symptoms of the disease, Brandon Jutras' research team at Virginia Polytechnic Institute and State University, USA, has in recent years been looking at what drives Lyme arthritis. Prof. Allen Steere, who has already contributed to the discovery and naming of Lyme disease, was also involved in the research.

Signs in cellular walls

The researchers were particularly interested in why the treatment of Lyme arthritis has no effect on some patients and why symptoms persist even without signs of infection. The authors write: "It is believed that excessive, misregulated immune responses of the host play an important role, but these mechanisms are not yet fully understood".

For their research, the scientists used samples from Lyme patients who did not respond to antibiotic treatment and focused particularly on peptidoglycan due to the unusual chemical properties of the macromolecule in Borrelia burgdorferi.

This variant does not have the necessary enzymes to reproduce peptidoglycan, but the macromolecule disintegrates into freely floating fragments. The research team wondered whether this fragmentation is responsible for the continuation of inflammations, even if the bacteria were destroyed by antibiotics.

The immune system reaction

The researchers showed that a counter-reaction to the fragments occurs in the immune system. The markers for this immune activity were significantly higher in the joint fluid of the participants than in their blood serum.

For more extensive investigations, the scientists purified this special form of the macromolecule and removed all traces of bacteria. The samples were administered to mice with joint disease within 24 hours.

Jutras hopes to use these findings to develop treatment methods that can destroy peptidoglycan in the joints of Lyme disease patients that have been altered by Lyme disease: "Our discovery will support research in improving diagnostic tests and could enable completely new treatment methods for patients with Lyme arthritis".

The researchers also believe that their findings could be useful in areas other than Lyme arthritis. "Since Borrelia burgdorferi releases immunizing peptidoglycan fragments during growth, there is also a potentially important role in the immunopathogenesis of other manifestations of Lyme disease.

Next, Jutras hopes to gain better insights into how the chemistry of the present peptidoglycan form is structured and why the macromolecule can remain in body tissue for so long.

Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis
Brandon L. Jutras, Robert B. Lochhead, Zachary A. Kloos, Jacob Biboy, Klemen Strle, Carmen J. Booth, Sander K. Govers, Joe Gray, Peter Schumann, Waldemar Vollmer, Linda K. Bockenstedt, Allen C. Steere, Christine Jacobs-Wagner
Proceedings of the National Academy of Sciences Jul 2019, 116 (27) 13498-13507; DOI:10.1073/pnas.1904170116

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