Although Lyme disease is easiest to treat in its early stages, current tests often miss infections during that critical period and cannot determine whether the bacteria is still present or was eliminated years ago. A new study led by Tufts University School of Medicine suggests that a group of immune molecules called anti-lipid antibodies may be able to address these shortcomings.
The results of this study were published in the Journal of the American Society for Microbiology. Infectious diseases and immunitythis could lead to improved tests to identify Lyme disease early if antibiotics can best prevent the more debilitating disease. It could also help clinicians better identify patients who continue to experience symptoms of infection after treatment, potentially discovering new drug targets to help patients.
Nearly half a million Americans are diagnosed with and treated for Lyme disease each year. Caused by bacteria Borrelia burgdorferi The disease is spread by the bite of an infected black-legged tick (also known as a deer tick) and can cause arthritis, neurological problems, and heart complications if untreated. Although most patients recover after treatment, an estimated 10% to 20% continue to experience symptoms such as fatigue, pain, and cognitive impairment, a condition known as post-treatment Lyme disease syndrome.
Current Lyme disease tests look for antibodies that the immune system produces in response. Borrelia burgdorferi Bacteria.
The problem is that these antibodies do not have the right properties to be clinically useful. That’s because these antibodies can take weeks to appear and often remain detectable for years after the bacteria has disappeared. ”
Peter Gwynn, study lead author and research assistant professor, Tufts University School of Medicine
Previous research by Gwinn and colleagues, part of the Tufts University Lyme Disease Initiative, showed that Lyme disease bacteria elicit antibodies against certain lipids, or fats, that they borrow from their human hosts. Unlike the antibodies used in current Lyme disease testing, these anti-lipid antibodies appear early in infection and decline after successful treatment.
Building on these early findings, researchers analyzed blood samples from 199 people diagnosed with Lyme disease. This included people whose symptoms persisted for months or even years after treatment. The researchers tracked anti-lipid antibody levels over time and compared them with samples from healthy volunteers and people with conditions similar to Lyme disease syndrome after treatment, including lupus, multiple sclerosis, fibromyalgia, long-term COVID-19 infection, and chronic fatigue syndrome.
Multiple analyzes identified three antilipid antibodies that are present at high levels during Lyme disease infection. Two of these antibodies, anti-phosphatidic acid (αPA) and anti-phosphatidylserine (αPS), are elevated at the time of diagnosis even in some patients who have not yet tested positive on standard Lyme disease tests, suggesting that these antibodies may help detect the infection early. Patients with persistent symptoms after treatment were also more likely to have elevated αPS levels several months later.
According to the researchers, this data suggests that while transient increases in these antilipid antibodies may indicate a new Lyme disease infection, sustained increases in αPS are associated with ongoing symptoms in some patients.
The new study also showed that while elevated alphaPS levels are common in many patients with persistent Lyme disease symptoms, they are rarely seen in patients with other autoimmune or chronic conditions that resemble Lyme disease syndrome after treatment.
The researchers stress that the findings do not yet support new clinical trials. Larger studies are needed to determine how accurately the markers identify infection and predict long-term symptoms.
To answer these questions, Gwynn and co-author Linden Hu, Paul and Elaine Cherbinski Professor of Immunology at Tufts University School of Medicine, are looking to a large, Tufts-led multicenter study that follows patients for up to 15 months after being diagnosed with Lyme disease. The research team will use the samples collected in this trial to assess whether anti-lipid antibodies can reliably identify early infections and distinguish between patients with prolonged symptoms.
Although the newly published study had a relatively small comparison group, Gwinn said the findings suggest that another type of immune system dysfunction may be causing Lyme disease’s persistent symptoms. “If further studies, including clinical trials, confirm these differences, they could point researchers toward new treatments for people who are treated for Lyme disease and still suffer from long-term symptoms,” he said.
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Reference magazines:
Shrestha, M. Others. (2026). Antiphospholipid antibodies in acute and post-treatment Lyme disease. Infectious diseases and immunity. DOI: 10.1128/IAI.00192-26. https://journals.asm.org/doi/10.1128/iai.00192-26
