Scientists have identified a trio of immune molecules that could help doctors catch Lyme disease earlier and distinguish patients whose symptoms persist long after treatment ends. The discovery, led by researchers at Tufts University School of Medicine, may pave the way for better tests that work during the critical early window when antibiotics are most effective.
Lyme disease is easiest to treat soon after infection, but standard tests often miss cases during that narrow period. Current tests look for antibodies the immune system makes in response to the bacterium Borrelia burgdorferi. These antibodies can take weeks to appear and often remain detectable for years after the infection clears, making it difficult to tell whether someone has an active infection or is dealing with lingering aftereffects. The new research focuses on a different type of immune response: antibodies against lipids, or fats, that the bacteria steal from their human hosts. Unlike standard antibodies, these anti-lipid antibodies appear early in infection and drop off after successful treatment.
In the study, published in the journal Infection and Immunity, researchers analyzed blood samples from 199 people diagnosed with Lyme disease, including some with symptoms that persisted for months or years after treatment. They tracked anti-lipid antibody levels over time and compared them with samples from healthy volunteers and people with conditions that can mimic post-treatment Lyme disease syndrome, such as lupus, multiple sclerosis, fibromyalgia, long COVID and chronic fatigue syndrome. Three anti-lipid antibodies turned up at higher levels during Lyme infection. Two of them, anti-phosphatidic acid (αPA) and anti-phosphatidylserine (αPS), were elevated at diagnosis even in some patients who had not yet tested positive on standard tests. Patients with lingering symptoms after treatment were also more likely to have elevated αPS levels months later. Notably, elevated αPS levels were common among patients with persistent symptoms but largely absent in those with other autoimmune and chronic conditions.
What the Findings Mean for Patients
Researchers say a temporary rise in these antibodies may point to a new infection, while persistent elevation of αPS is linked to ongoing symptoms in some patients. “Existing tests for Lyme disease are nowhere near where they should be in some important areas: detecting infections early, providing proof of cure, differentiating new from historic infections, and testing for chronic disease,” said study senior author Peter Gwynne of the Tufts Lyme Disease Initiative. The team found that anti-lipid antibodies appear earlier than traditional diagnostic antibodies, and their levels rise and fall more dynamically, making them potentially useful for tracking whether a patient is getting better after treatment.
The researchers caution that the findings do not yet support a new clinical test. Larger studies are needed to confirm how accurately the markers detect infection and predict long-term symptoms. To answer those questions, Gwynne and co-author Linden Hu are turning to a large multi-institution trial that follows patients for up to 15 months after diagnosis. Using samples from that trial, the team plans to test whether anti-lipid antibodies can reliably identify early infections and predict which patients develop prolonged symptoms. “If confirmed by further studies like the clinical trial, those differences could point researchers toward new therapies for people experiencing long-lasting symptoms despite being treated for Lyme disease,” Gwynne said. The work was supported by the NIH, the Department of Defense, and the Bay Area Lyme Foundation.