Amsterdam institute for Immunology and Infectious diseases

Which genes and genetic variations play a role in Lyme disease, influencing sensitivity, severity, and duration? Researchers from Amsterdam UMC, in collaboration with Radboudumc, RIVM, and CiiM, have published findings in BMC Infectious Diseases and Nature Communications, identifying 31 new genetic loci that influence the disease and a new gene variant that increases susceptibility.

Lyme disease (Lyme borreliosis) is caused by a tick bite that transmits the bacterium Borrelia burgdorferi to humans. However, not everyone is equally susceptible or sensitive to Lyme disease. Some may not notice it at all, while others become ill. Timely antibiotic treatment cures most patients. However, some continue to experience symptoms such as fatigue, cognitive impairments, and pain, referred to as post-treatment Lyme disease
syndrome. These differences may be due to the interaction between the human immune system (the host) and the invading organisms (the guests). Innate and acquired immune responses to Borrelia burgdorferi partly determine whether an infection is effectively cleared. This prompted researchers from Amsterdam UMC, Radboudumc, RIVM, and CiiM to further analyze the genetic-immunological aspects of Lyme disease.

Increased susceptibility

The results of a genome-wide association study (GWAS) were recently published in BMC Infectious Diseases. Data from over 1,100 Lyme disease patients from the Dutch LymeProspect study were analyzed to see if small genetic variations influence susceptibility to this infection. Indeed, they do. Researchers found a previously unknown genetic variant that increases the risk of Lyme disease. People with this variant are slightly more susceptible to the disease. They also show a higher anti-inflammatory response and lower antibody production against Borrelia burgdorferi, possibly slowing down the clearance of the bacterium. This is an important genetic-immunological insight for future Lyme disease immunity research.

Genes and the immune system

Cytokines play an important role in the human immune system, acting as messengers between various immune cells. If they do not function properly, for example if they are produced too scarcely, infectious agents may not be effectively cleared. On the other hand, if they are produced too abundantly, excessive inflammation in affected organs may occur, resulting in health complaints and clinical signs. To gain more insight in these processes in Lyme disease, the research group mapped cytokine activity in over 1,000 patients. "We did this before or during, as well as after they received antibiotic treatment," says Joppe Hovius, professor of Infectious Diseases at the Amsterdam University Medical Center. "Through the involved cytokines, we identified 34 specific places in the genome, called gene loci, involved in the immune response of Lyme disease patients. Of these, 31 were previously unknown." This information not only provides more insight into the genes involved in the immune response to Lyme disease, but also to other diseases where the immune system plays a role. Prof. Hovius emphasizes: “this is truly a collaborative effort, where complementary expertise of all partners involved was the key to success.”

Excellent basis for further research

The research results clearly show how immune responses are determined by genetics. Because the results are based on a large number of patients, they form an excellent basis for further research, such as investigating the effect of different variants of the involved genes on the severity of Lyme disease or the development of post-treatment Lyme disease syndrome..

Publications

Publication in Nature Communications: A comprehensive genetic map of cytokine responses in Lyme borreliosis- Javier Botey-Bataller, Hedwig D. Vrijmoeth, Jeanine Ursinus, Bart-Jan Kullberg, Cees C. van den Wijngaard, Hadewych ter Hofstede, Ahmed Alaswad, Manoj K. Gupta, Lennart M. Roesner, Jochen Huehn, Thomas Werfel, Thomas F. Schulz, Cheng-Jian Xu, Mihai G. Netea, Joppe W. Hovius, Leo A. B. Joosten & Yang Li https://doi.org/10.1038/s41467-024-47505-z

Publication in BMC Infectious Diseases: Genome-wide analyses in Lyme borreliosis: identifcation of a genetic variant associated with disease susceptibility and its immunological implications- Hedwig D. Vrijmoeth, Jeanine Ursinus, Javier Botey‑Bataller, Yunus Kuijpers, Xiaojing Chu, Freek R. van de Schoor, Brendon P. Scicluna, Cheng‑Jian Xu, Mihai G. Netea, Bart Jan Kullberg, Cees C. van den Wijngaard, Yang Li, Joppe W. Hovius & Leo A. B. Joosten https://doi.org/10.1186/s12879-024-09217-z