What genes and genetic variations play a role in Lyme disease, such as susceptibility, severity and duration? Researchers from Radboudumc, Amsterdam UMC, RIVM and CiiM publish in BMC Infectious Diseases and Nature Communications 31 new genetic sites that influence and a new gene variant that confers increased susceptibility to the disease.
Lyme disease (Lyme borreliosis) is caused by a tick bite in which the bacterium Borrelia burgdorferi is transmitted to humans. Not everyone is equally susceptible or susceptible to the infection. Some do not notice it, while others become ill. Timely treatment with antibiotics brings healing to most patients. Still, a group of patients maintain symptoms such as fatigue, cognitive impairment and pain. As with other infectious diseases, this difference may have to do with the interaction between a person's defenses (the host) and the invading organisms (the guests). Congenital and acquired immune responses against the Borrelia bacteria co-determine whether an infection is cleared quickly and well or not. Sufficient reason for researchers from Radboudumc, Amsterdam UMC, RIVM and CiiM to further analyze genetic-immunological aspects in Lyme disease.
Increased sensitivity
The results of a genome wide association study (GWAS) were recently published in BMC Infectious Diseases. Data from over 1100 patients with Lyme disease from the Dutch LymeProspect study were examined to see whether small genetic variations influence susceptibility to this infection. Hedwig Vrijmoeth, physician-researcher in the Radboudumc: “That indeed turned out to be the case. We found a hitherto unknown variant that increases the risk of Lyme disease. So people with this variant are slightly more susceptible to the disease. In them we also see a higher anti-inflammatory response and a lower production of antibodies against the Borrelia bacteria. Possibly this also causes the bacteria to be cleared more slowly. In any case, it is an important genetic-immunological effect to take into account in future scientific research on defense against lyme disease.”
Genes and immune system
In the human immune system, cytokines play an important role. Cytokines are small proteins that act as messengers between various cells of the immune system. If they do not work properly, if there are too many or too few, the Borrelia bacteria may not be cleared properly. Or possibly it is just attacked extra hard or other reactions and symptoms occur. To find out more, the research group mapped cytokine activity in more than 1,000 patients. “We did that before, or while they were receiving antibiotic treatment and again afterwards,” says Joppe Hovius, professor of Infectious Diseases at the Amsterdam UMC. “Through the cytokines involved, we were also able to identify 34 specific sites in the genome, so-called gen loci, that are involved in the immune response of Lyme disease patients. Of these, 31 were not yet known.” Leo Joosten, professor of inflammatory responses at Radboudumc explains: “This not only gives us more insight into the genes involved in the immune response to Lyme disease, but also in other diseases in which the immune system plays a role.”
Excellent basis for follow-up research
“Our research results clearly show how immune responses are determined by genetics,” said Yang Li, professor of Computational Biology at the German Centre for Individualized Infection Medicine (CiiM). “Because our results are based on a large number of patients, they provide an excellent basis for further research, for example to investigate the effect of different variants of the genes involved on the disease severity of Lyme disease.”
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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
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Pieter Lomans
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