{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:31:27Z","timestamp":1791415887506,"version":"4.3.3"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,2,12]],"date-time":"2016-02-12T00:00:00Z","timestamp":1455235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T00:00:00Z","timestamp":1456876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Swartz Foundation"},{"DOI":"10.13039\/100013479","name":"Bay Area Lyme Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013479","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stabler Foundation"},{"name":"Lyme Research Alliance"},{"name":"Lyme Disease Research Foundation, Inc."},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["HL105704"],"award-info":[{"award-number":["HL105704"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["P30-AR05350"],"award-info":[{"award-number":["P30-AR05350"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001316","name":"Abbott Laboratories","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,3,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lyme disease is a tick-borne illness caused by the bacterium\n                    <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>\n                    , 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\u00a0months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3\u00a0weeks 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\u00a0months 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 \u201cwindow period\u201d of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    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\u00a0months 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\u00a0weeks 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.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00100-16","type":"journal-article","created":{"date-parts":[[2016,2,13]],"date-time":"2016-02-13T06:24:14Z","timestamp":1455344654000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":82,"title":["Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease"],"prefix":"10.1128","volume":"7","author":[{"given":"Jerome","family":"Bouquet","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Soloski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Swei","sequence":"additional","affiliation":[{"name":"Department of Biology, San Francisco State University, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Cheadle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scot","family":"Federman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Noel","family":"Billaud","sequence":"additional","affiliation":[{"name":"Qiagen Bioinformatics, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison W.","family":"Rebman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beniwende","family":"Kabre","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Halpert","sequence":"additional","affiliation":[{"name":"Qiagen Bioinformatics, Redwood City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meher","family":"Boorgula","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Aucott","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2915-2094","authenticated-orcid":false,"given":"Charles Y.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60103-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu397"},{"key":"e_1_3_2_4_2","first-page":"993","article-title":"Three sudden cardiac deaths associated with Lyme carditis\u2014United States, November 2012-July 2013","volume":"62","author":"Centers for Disease C, Prevention","year":"2013","unstructured":"Centers for Disease C, Prevention. 2013. Three sudden cardiac deaths associated with Lyme carditis\u2014United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep 62:993\u2013996. http:\/\/www.cdc.gov\/mmwr\/preview\/mmwrhtml\/mm6249a1.htm.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2007.12.011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-9-79"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2013.01.008"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21681"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018220"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit735"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2013.11.002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/508667"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093243"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ185"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071462"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2012.0283"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004869"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00775-14"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2012.742535"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001289"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.11.014"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9352"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000366414"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000659"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2008.07.008"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636387"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.01.003"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2014.929563"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1086\/523828"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22131"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2009.06.003"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004976"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.2741\/Wang"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv310"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.37732"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.07.005"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(03)00308-5"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.12.9.1036-1040.2005"},{"key":"e_1_3_2_39_2","first-page":"251","article-title":"Rheumatoid arthritis and systemic lupus erythematosus as immune complex diseases","volume":"67","author":"Weissmann G","year":"2009","unstructured":"Weissmann G. 2009. Rheumatoid arthritis and systemic lupus erythematosus as immune complex diseases. Bull NYU Hosp Jt Dis 67:251\u2013253.","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017287"},{"key":"e_1_3_2_41_2","first-page":"590","article-title":"Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease","volume":"44","author":"Centers for Disease Control and Prevention","year":"1995","unstructured":"Centers for Disease Control and Prevention. 1995. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 44:590-591. http:\/\/www.cdc.gov\/mmwr\/preview\/mmwrhtml\/00038469.htm.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-S2-S11"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6364"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002924"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.2.1172"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-2-38"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-02-002477"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2343"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006803"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/19.2.185"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00100-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00100-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T21:04:11Z","timestamp":1646687051000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00100-16"}},"subtitle":[],"editor":[{"given":"Alan G.","family":"Barbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,3,2]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,3,2]]}},"alternative-id":["10.1128\/mBio.00100-16"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00100-16","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726144707.793514872","asserted-by":"object"}]},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,2]]},"assertion":[{"value":"2016-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00100-16"}}