Longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute Lyme disease

Jerome Bouquet, Mark J. Soloski, Andrea Swei, Chris Cheadle, Scot Federman, Jean Noel Billaud, Alison W. Rebman, Beniwende Kabre, Richard Halpert, Meher Boorgula, John N. Aucott, Charles Y. Chiu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere00100-16
JournalmBio
Volume7
Issue number1
DOIs
StatePublished - Feb 12 2016

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Lyme Disease
Gene Expression Profiling
Acute Disease
Transcriptome
Anti-Bacterial Agents
Infection
Biological Markers
Genes
Tick-Borne Diseases
Borrelia burgdorferi
Toll-Like Receptors
Ticks
Antibody Formation
Communicable Diseases
Longitudinal Studies
B-Lymphocytes
Chronic Disease
Up-Regulation
Bacteria
T-Lymphocytes

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute Lyme disease. / Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher; Aucott, John N.; Chiu, Charles Y.

In: mBio, Vol. 7, No. 1, e00100-16, 12.02.2016.

Research output: Contribution to journalArticle

Bouquet, J, Soloski, MJ, Swei, A, Cheadle, C, Federman, S, Billaud, JN, Rebman, AW, Kabre, B, Halpert, R, Boorgula, M, Aucott, JN & Chiu, CY 2016, 'Longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute Lyme disease' mBio, vol 7, no. 1, e00100-16. DOI: 10.1128/mBio.00100-16

Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher; Aucott, John N.; Chiu, Charles Y. / Longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute Lyme disease.

In: mBio, Vol. 7, No. 1, e00100-16, 12.02.2016.

Research output: Contribution to journalArticle

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