Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with
antibiotics. To gain insights into the molecular basis of acute
Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29
Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of
Lyme disease following the acute phase of
infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early
Lyme disease prior to
antibiotic therapy was characterized by marked upregulation of
Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of
therapy,
Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated
chronic diseases. No differential gene expression signature was observed between
Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in
Lyme disease suggests that a panel of selected human host-based
biomarkers may address the need for sensitive clinical diagnostics during the "window period" of
infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets.
IMPORTANCE:
Lyme disease is the most common
tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite
antibiotic treatment. To better understand the role of the human host response in acute
Lyme disease and the development of post-treatment symptoms, we conducted the first longitudinal gene expression (transcriptome) study of patients enrolled at the time of diagnosis and followed up for up to 6 months
after treatment. Importantly, we found that the gene expression signature of early
Lyme disease is distinct from that of other acute
infectious diseases and persists for at least 3 weeks following
infection. This study also uncovered multiple previously undescribed pathways and genes that may be useful in the future as human host
biomarkers for diagnosis and that constitute potential targets for the development of new
therapies.