Immunosequencing T-Cell Receptor Repertoires Helps Diagnose Lyme Disease

Lyme disease is the most common tick-borne illness in the US, but severe illness can be prevented if it is diagnosed and treated early on. However, some patients do not present with the typical erythema migrans rash, making diagnosis more difficult.

Principal investigator John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center; and investigators from the Bay Area Lyme Foundation and Adaptive Biotechnologies collaborated on a diagnostic approach for Lyme disease based on the T-cell response to Borrelia burgdorferi, the bacteria species that most frequently causes the disease.

By immunosequencing T-cell receptor (TCR) repertoires in blood samples from three independent cohorts of patients, the investigators were able to detect early Lyme disease with 99% specificity.

Contagion conducted a virtual Q&A with Adaptive Biotechnologies and key author Sudeb C. Dalai, MD, PhD, to gain further insight into the late-breaking study, “Immunosequencing of the T-Cell Receptor Repertoire Reveals Signatures Specific for Diagnosis and Characterization of Early Lyme Disease,” which was presented virtually at IDWeek 2021.

Contagion: Can you expand on the impetus for this study?

Adaptive Biotechnologies: Early diagnosis and treatment can prevent the development of severe illness and late manifestations of Lyme. The ImmuneSense™ Lyme study was designed to determine if a T-cell test could be used to detect Lyme disease earlier and more accurately than antibody testing or the Standard Two-Tiered Testing (STTT), which is the current standard of care. The sensitivity of STTT varies between 25-50%, with particularly poor performance in the early days of infection.

Contagion: Can you highlight the key findings of the study?

Adaptive Biotechnologies: The clinical study conducted by Greissl et al. utilized Adaptive’s TCR sequencing and Microsoft’s AI and machine learning to identify a clinical signal for early Lyme disease based on evaluation of the T-cell response to B. burgdorferi infection. The T-cell test was demonstrated to be nearly two times more sensitive compared to STTT (antibody testing) in early Lyme disease and three times more sensitive in the first few days of symptom onset. In individuals who were initially STTT-negative but ultimately converted to having a positive antibody test, nearly 40% of them were identified as positive by T-cell testing prior to seroconversion, supporting previous observations that the T-cell response is detectable before the antibody response.

Contagion: What is the main takeaway for clinicians?

Adaptive Biotechnologies: Adaptive’s TCR repertoire characterization demonstrated significantly greater sensitivity in identifying early Lyme disease compared to STTT. Although positivity for both testing methods wane with time after treatment, sensitivity of T-cell testing was ~20% greater than that of STTT at baseline and 6 months posttreatment. T-cell testing provides an alternative approach to measure the immune response to B. burgdorferi infection, especially in patients during the early stages of disease when STTT sensitivity is limited.

Contagion: What is next for this line of research?

Adaptive Biotechnologies: We’ll evaluate the clinical utility of the T-cell test relative to standard of care tests. The current study demonstrated the ability of the T-cell test to support a diagnosis of early Lyme disease in individuals who had clinically diagnosed Lyme disease through presence of erythema migrans rash (bullseye rash). Additional studies are needed to evaluate the advantages of T-cell testing in individuals who have an atypical or absent rash, individuals who may present with a wider range of symptoms, as well as those presenting in later stages of Lyme disease.