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Research team discovers gene variant and genes involved in immune regulation that are responsible for the outbreak of Lyme disease
Lyme disease is the most common disease transmitted by tick bites in Germany. Whether a particular genetic predisposition plays a role in the development of the disease and which immunological processes in the body are involved is not yet sufficiently understood. A research team from the Centre for Individualised Infection Medicine (CiiM), a joint institution of the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), has now discovered a responsible gene variant and the immune parameters involved in cooperation with Radboud University Hospital (Radboundumc; Radboud Universitair Medisch Centrum) and Amsterdam UMC (both in the Netherlands). The researchers have published their findings in two studies. These have been published in the journals Nature Communications and BMC Infectious Diseases.
If a tick is infected with the pathogen Borrelia burgdorferi s. l. (sensu lato = in the broader sense), these bacteria can be transmitted to humans through a tick bite and cause illness. Various organ systems can be affected: the skin, the nervous system or the joints. "An infection with Borrelia does not always lead to illness, and in case of the outbreak of Lyme disease it can usually be successfully treated with antibiotics. However, as our cooperation partners have discovered, some of those affected develop persistent symptoms such as fatigue, cognitive impairment or pain despite antibiotic treatment," says Prof. Yang Li, Director of the CiiM and Head of the "Bioinformatics of Individualised Medicine" Department at the HZI. "In order to find additional starting points for the development of effective therapies for the treatment of Lyme disease in the future, it is first important to better understand the genetic and immunological mechanisms responsible for the development of the disease."
To this end, the research team analyzed the gene patterns of more than 1,000 Lyme disease patients and compared them with the gene patterns of non-infected individuals. "The aim was to identify specific gene variants that are directly associated with the disease," explains Javier Botey-Bataller, research associate at CiiM and one of the first authors of the two studies. "We were indeed able to identify a special, previously unknown gene variant in Lyme disease patients." The research team carried out various cell biological and immunological tests to find out what specific physiological consequences this genetic predisposition has. "On the one hand, we were able to show that anti-inflammatory processes in the body were reduced in the presence of this gene variant. This means that inflammation and symptoms of Lyme disease may last longer," explains Li. The researchers also discovered that patients with this gene variant produced significantly fewer antibodies against Borrelia. They suspect that the bacteria cannot be attacked efficiently as a result and that the disease therefore lasts longer.
"We were also able to identify 34 different gene loci that are involved in the regulation of the immune response of Lyme disease patients via messenger substances, so-called cytokines, and that could also play an important role in other immune-mediated diseases such as allergies," says Botey-Bataller. In research, all genes of the human genome are recorded in a so-called gene map. Each gene has its individual position there, which is referred to as a gene locus. "Our study results clearly show how immune responses are determined by genetics," says Li. "Since our study results are based on an extremely broad database due to the large cohort, they provide an excellent basis for further research approaches, for example to investigate the effect of different variants of the genes involved on the disease severity of Lyme disease."
The incidence of Lyme disease has increased in the northern hemisphere in recent years. The research team assumes that a further increase must be expected in the future, even against the backdrop of climate change. This is because generally milder temperatures are likely to prolong the tick season and increase the distribution area of ticks. The result: more tick bites and therefore more possible cases of Lyme disease. "With our study results, we were able to gain important insights into the genetic and immunological processes that favor the development of Lyme disease. We hope that we have been able to pave the way for the development of effective treatments for Lyme disease sufferers with long-lasting symptoms," says Li.
This press release is also available on our homepage: https://www.helmholtz-hzi.de/en/media-center/newsroom/news-detail/lyme-disease-p....
Centre for Individualized Infection Medicine:
The CiiM is a joint venture of the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH) and is the first research institute explicitly dedicated to develop personalized medicine for infections. The departments and groups of the CiiM are working towards the vision of treating infectious patients in an adapted and optimized way according to the specific needs and requirements of each individual. To achieve this, CiiM is dedicated to researching individual characteristics and their impact on susceptibility to infection or treatment success with available therapies. https://www.ciim-hannover.de/en/
Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and its other sites in Germany are engaged in the study of bacterial and viral infections and the body’s defence mechanisms. They have a profound expertise in natural compound research and its exploitation as a valuable source for novel anti-infectives. As member of the Helmholtz Association and the German Center for Infection Research (DZIF) the HZI performs translational research laying the ground for the development of new treatments and vaccines against infectious diseases. http://www.helmholtz-hzi.de/en
Contact:
Susanne Thiele, Spokesperson
susanne.thiele@helmholtz-hzi.de
Dr Charlotte Schwenner, Editor
charlotte.schwenner@helmholtz-hzi.de
Helmholtz Centre for Infection Research
Press and Communications
Inhoffenstr. 7
D-38124 Braunschweig
Germany
Phone: +49 531 6181-1400; -1406
Botey-Bataller, J., Vrijmoeth, H.D., Ursinus, J. et al. A comprehensive genetic map of cytokine responses in Lyme borreliosis. Nat Commun 15, 3795 (2024). https://doi.org/10.1038/s41467-024-47505-z
Vrijmoeth, H.D., Ursinus, J., Botey-Bataller, J. et al. Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications. BMC Infect Dis 24, 337 (2024). https://doi.org/10.1186/s12879-024-09217-z
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