The likelihood of developing Lyme disease depends on genetics

Lyme disease is the most common disease transmitted by tick bites in Germany. It has not yet been sufficiently studied whether a certain genetic predisposition plays a role in the development of the disease and what immunological processes in the body are involved.

A research team from the Center for Individualized Infectious Medicine (CiiM), a joint institution of the Helmholtz Center for Infection Research (HZI) and the Hannover Medical School (MHH), in collaboration with the Radboud University Hospital and the Amsterdam University Medical Center (both in the Netherlands) has now opened a responsible genetic variant and immune parameters involved.

If the tick is infected with the pathogen Borrelia burgdorferi s. L. (sensu lato = in a broad sense), these bacteria can be transmitted to humans through a tick bite and cause disease. Various organs may be affected: skin, nervous system or joints.

"Borrelia infection does not always lead to illness, and when Lyme disease occurs, it can usually be successfully treated with antibiotics. However, our collaborating partners have found that some victims develop persistent symptoms, such as fatigue, cognitive impairment, or pain, despite for antibiotic treatment," says Professor Yang Li, director of CiiM and head of the Bioinformatics of Individualized Medicine department at HZI.

"To find additional starting points for the development of effective therapies for the treatment of Lyme disease in the future, it is important to better understand the genetic and immunological mechanisms responsible for the development of the disease." p>

Towards this end, the research team analyzed the genetic patterns of more than 1,000 Lyme disease patients and compared them with the genetic patterns of uninfected people. “The goal was to identify specific genetic variants directly associated with the disease,” explains Javier Botey-Bataliere, a researcher at CiiM and one of the first authors of the two studies.

"We were actually able to identify a specific, previously unknown genetic variant in patients with Lyme disease."

Identification of the rs1061632 variant associated with LB sensitivity. Overview of cohorts. 1107 DNA samples from LB patients were available for quality control and imputation, leaving a discovery group (n = 506) and a validation group (n = 557). B Manhattan plot of genome-wide significant variants associated with LB susceptibility in the discovery cohort. Photo: BMC Infectious Diseases (2024). DOI: 10.1186/s12879-024-09217-z

The research team conducted 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 the body's anti-inflammatory processes are reduced in the presence of this genetic variant. This means that inflammation and symptoms of Lyme disease may last longer,” explains Lee.

The researchers also found that patients with this genetic variant had significantly reduced levels of antibodies against Borrelia. They suggest that as a result, the bacteria cannot be effectively attacked and therefore the disease lasts longer.

"We were also able to identify 34 different gene loci that are involved in regulating the immune response of patients with Lyme disease through mediators such as cytokines, and which may also play an important role in other immune-mediated diseases such as allergies," says Botey-Bataliere.

In the study, all the genes of the human genome are recorded in the so-called genetic map. Each gene has its own individual position, which is called a gene locus. "Our study results clearly show how the immune response is determined by genetics," says Lee.

"Because our study results are based on an extremely broad database due to a large cohort, they provide an excellent basis for further research approaches, for example, to study the impact of different variants of the genes involved on the severity of Lyme disease."

The incidence of Lyme disease has increased in the northern hemisphere in recent years. The research team suggests that further increases can be expected in the future, even with climate change. This is because generally milder temperatures can extend the tick season and increase their distribution range.

The result: more tick bites and therefore more possible cases of Lyme disease. "With the results of our study, we have gained important insights into the genetic and immunological processes that contribute to the development of Lyme disease. We hope that we have paved the way for the development of effective treatments for Lyme disease sufferers with long-term symptoms," says Lee.

The researchers published their results in two studies, one in Nature Communications and another in BMC Infectious Diseases .