Diagnosing Lyme Disease made easier with novel test

Lyme Disease
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A research team from Tufts University has developed a novel test to make diagnosing Lyme Disease easier, thus resulting in more efficient treatment.

How does this test for diagnosing Lyme Disease work?

Researchers at Tufts University School of Medicine have identified a testing mechanism for diagnosing Lyme Disease that detects a specific type of antibody that infected individual’s bodies produce to fight against a substance the Lyme bacteria acquires from the host in order to grow.

Thus, scientists intend for the test to detect these autoantibodies – antibodies that mistakenly target and react with a person’s own tissues or organs – to provide clinicians with a method to diagnose the disease sooner, know whether treatment with antibiotics is working, and identify patients who have been re-infected.

Authors of the study include Peter Gwynne, Luke Clendenen, and Linden Hu of the school’s Department of Molecular Biology and Microbiology, and colleagues at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH).

This study was published on 15 March 2022 in the Journal of Clinical Investigation.

What is Lyme Disease?

Lyme Disease is caused by a bite from an infected tick, which frequently goes undetected unless a person notices the tell-tale rash that forms around the bite. It is caused by the bacterium Borrelia burgdorferi, which can often be treated with antibiotics. However, in 10-20% of cases, the disease’s impact can persist.

The infection was identified five decades ago along the Connecticut coast and spread across New England and the mid-Atlantic region – it currently affects approximately 500,000 people in the US every year. It has been noted to potentially lead to debilitating long-term complications, including arthritis, fatigue, mental impairment, and in the most severe cases, attacks on the heart and brain tissue.

What limitations exist with current testing methods?

“Testing to detect Lyme Disease exists, but it has limitations,” noted Gwynne, lead author of the study and Research Scientist at Tufts School of Medicine who received a Tufts Launchpad Accelerator award for his work on Lyme Disease. “Traditional Lyme tests can stay positive for prolonged periods of time after treatment – years or even a lifetime.

“As a result, for some individuals suffering from symptoms that resemble long-term Lyme Disease infection, clinicians are never sure whether the patient has persistent Lyme Disease, was cured, and then re-infected, or was cured and is suffering from something else.”

How was this novel test developed?

“We started this current work to learn how Borrelia burgdorferi acquires key nutrients, like fats, for growth,” said Gwynne. “The Lyme bacterium, despite being a very successful pathogen, is much more dependent than other bacteria on acquiring nutrients from its environment.”

“In the process of our research, we found that the organism takes fats called phospholipids directly from its surroundings in the host, and puts it on its surface,” added Hu, Vice Dean of Research at the school, and Paul and Elaine Chervinsky Professor of Immunology. “This finding led us to look to see if the direct use of a host fat by the bacteria might lead the immune system to recognise it as a foreign substance and create antibodies to it.”

While developing this test for diagnosing Lyme Disease, scientists discovered that both animals and patients infected with the Lyme bacterium developed autoantibodies to multiple phospholipids. Thus, because autoantibodies can be damaging to the host, these autoantibodies are tightly regulated and tend to disappear quickly once the stimulating factor is removed.

“The antibodies also seem to develop much more quickly than traditional antibodies to the Lyme bacteria—likely because your body has previously created these autoantibodies and downregulated them,” explained Hu.

While current tests for diagnosing Lyme Disease make it difficult to diagnose reinfection or successful treatment, Gwynne noted: “The antiphospholipid autoantibodies—because of their quick increase and quick resolution with treatment—can fill these gaps as a novel additional test.

“They may make it possible to tell whether treatment has eradicated the Lyme Disease bacteria. And they therefore also make it possible to tell if a patient with a prior infection now has a new infection.”

Both Gwynne and Hu have a provisional patent pending illustrating the utilisation of antiphospholipid antibodies in diagnosing Lyme Disease. Their intention is that if their discovery is continued with further research, a diagnostic company could begin development of a commercially available version of their test within a couple of years.

What are the limitations of this novel test?

A potential issue that has not been examined in this research is whether these autoantibodies can identify a subset of patients who will develop persistent symptoms of Lyme Disease after treatment.

Up to 20% of patients can develop persistent symptoms after suffering from Lyme Disease, and diagnosis of these patients is currently only carried out by clinical symptoms. This means it is likely that patients with different causes of their symptoms are grouped together, and treatment trials in patients with persistent Lyme Disease are unlikely to exhibit benefits if that occurs.

“Antiphospholipid antibodies are commonly seen in autoimmune diseases like lupus and are associated with blood clots and persistent inflammation that causes other disease conditions,” concluded Hu. “Many of the persistent symptoms in patients who continue to have symptoms after being diagnosed with Lyme Disease are similar to those autoimmune diseases.”

“If there ends up being a link between having persistent Lyme symptoms and these autoantibodies, this would be the first test that could be used to distinguish a group of patients who have persistent Lyme Disease. It would allow us to test specific new therapies targeted to a defined mechanism.”

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