Researchers at Tufts University School of Medicine have identified a group of immune antibodies that appear earlier than current laboratory markers of Lyme disease. The new markers may also help identify a subset of patients with persistent symptoms after treatment, raising the prospect of new diagnostic tools for both acute and post-treatment disease.
Current laboratory diagnosis of Lyme disease relies largely on antibodies against Borrelia burgdorferi. These tests perform well once the immune response is established, but are less sensitive during the first weeks of infection and cannot distinguish between active infection, past infection, and ongoing post-treatment symptoms. Around 10–20 percent of treated patients experience persistent symptoms, yet there are no validated biomarkers for post-treatment Lyme disease (PTLD).
In the new study, published in Infection and Immunity, investigators analyzed blood samples from multiple US Lyme disease cohorts, including patients sampled at diagnosis and followed for up to a year, alongside individuals with long-standing PTLD. They measured antibodies directed against phospholipids, a class of fats found in cell membranes that B. burgdorferi acquires from its host.
Three antibody types increased during infection, but two – those targeting phosphatidic acid and phosphatidylserine – were already elevated when patients first presented with the characteristic erythema migrans rash, even though many remained negative by conventional two-tier serology. This suggests these markers could complement existing tests during the diagnostic window when current assays are less sensitive.
Rather than replacing established serology, the authors propose incorporating antiphospholipid antibodies into multi-marker testing strategies to improve early detection while maintaining specificity.
The study also found that most patients' antiphospholipid antibody levels declined after treatment. However, a subgroup of patients with long-term PTLD showed persistently raised antibodies against phosphatidylserine, a pattern that was not observed in comparison groups with fibromyalgia, systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, myalgic encephalomyelitis/chronic fatigue syndrome, or long COVID. Although the findings do not establish that these antibodies cause persistent symptoms, they suggest the marker could help identify a biologically distinct subgroup of patients for future studies.
The authors note that larger validation studies will be needed before clinical implementation. They also suggest that serial measurement of these antibodies could eventually play a role similar to non-treponemal testing in syphilis, providing laboratory support for monitoring disease activity alongside established Lyme diagnostics rather than replacing them.
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
