Study evaluates T-cell testing for Lyme disease
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T-cell testing was nearly twice as sensitive at identifying early Lyme disease compared with the standard two-tiered serologic testing and more than three times more sensitive in the first 4 days, researchers reported at IDWeek.
In 2019, the CDC recommended a new two-tier testing algorithm for Lyme disease — the most common vector-borne disease in the United States — that uses a second enzyme immunoassay in place of a western immunoblot assay.
Principal investigator John Aucott, MD, director of the Johns Hopkins Lyme Disease Research Center; and investigators from the Bay Area Lyme Foundation and Adaptive Biotechnologies, including Sudeb C. Dalai, MD, PhD, senior medical director, collaborated on a diagnostic approach for Lyme disease based on the T-cell response to Borrelia burgdorferi.
They immunosequenced T-cell receptor repertoires in blood samples from three cohorts of patients with confirmed or clinically diagnosed early Lyme disease to identify 251 Lyme disease-associated T-cell receptors.
“Early diagnosis and treatment can prevent the development of severe illness and late manifestations of Lyme disease,” Dalai told Healio. “The sensitivity of standard 2-tiered testing (STTT), the current standard of care, varies between 25% and 50%, with particularly poor performance in the early days of infection.”
Using these T-cell receptors, the authors trained a classifier that identified early Lyme disease with 99% specificity, the researchers reported. Biologic specificity was evaluated by correlating T-cell receptors assay scores with clinical measures and mapping the antigen specificity of T-cell receptors with B. burgdorferi antigens, they said.
According to the researchers, T-cell receptor testing demonstrated a 1.9-fold increase in sensitivity compared with the two-tiered testing (56% vs. 30%) and a 3.1-fold increase in sensitivity within 4 days of symptom onset (44% vs. 14%).
“In individuals who were initially STTT-negative but ultimately converted to having a positive antibody test, 37% 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,” Dalai said.
According to the abstract, a subset of Lyme disease-associated T-cell receptors mapped to B. burgdorferi antigens, “demonstrating the high specificity” of T-cell-based testing.
“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,” Dalai said.
Perspective
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It’s an interesting new approach that needs to be assessed in multiple different settings/populations before its utility can be fully understood. However, even in this study, the “improved” sensitivity of the test results is not high enough — 44% or 56%, depending on timing — to be especially useful clinically.
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Dalai SC, et al. Abstract 14. Presented at: IDWeek; Sept. 29-Oct. 3, 2021 (virtual meeting).
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