Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease
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 ensuin...
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2016-02-01
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doaj-ecd59950ca224b5fb640a03471b2f7ce2021-07-02T03:06:28ZengAmerican Society for MicrobiologymBio2150-75112016-02-0171e00100-1610.1128/mBio.00100-16Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme DiseaseJerome BouquetMark J. SoloskiAndrea SweiChris CheadleScot FedermanJean-Noel BillaudAlison W. RebmanBeniwende KabreRichard HalpertMeher BoorgulaJohn N. AucottCharles Y. ChiuLyme 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.http://mbio.asm.org/cgi/content/full/7/1/e00100-16 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease mBio |
author_facet |
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 |
author_sort |
Jerome Bouquet |
title |
Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease |
title_short |
Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease |
title_full |
Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease |
title_fullStr |
Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease |
title_full_unstemmed |
Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease |
title_sort |
longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute lyme disease |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2016-02-01 |
description |
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. |
url |
http://mbio.asm.org/cgi/content/full/7/1/e00100-16 |
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