{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:00:27Z","timestamp":1771023627744,"version":"3.50.1"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region Kalmar County (IT), Futurum-Academy for Healthcare and Division of Medical Diagnostics, Region J\u00f6nk\u00f6ping County, Interreg IVA Program ScandTick","award":["167226"],"award-info":[{"award-number":["167226"]}]},{"name":"Interreg V program ScandTick Innovation","award":["project ID. 20200422, reference no. 2015-29 000167"],"award-info":[{"award-number":["project ID. 20200422, reference no. 2015-29 000167"]}]},{"name":"The Medical Research Council of Southeast Sweden","award":["FORSS-475511"],"award-info":[{"award-number":["FORSS-475511"]}]},{"name":"the foundation for medical research of the \u00c5land cultural foundation"},{"DOI":"10.13039\/100010113","name":"Wilhelm and Else Stockmann Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010113","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Lyme serology does not readily discriminate an active Lyme borreliosis (LB) from a previous <jats:italic>Borrelia<\/jats:italic> infection or exposure. Here, we aimed to investigate a large number of immunological protein biomarkers to search for an immunological pattern typical for active LB, in contrast to patterns found in healthy blood donors, a proportion of whom were previously exposed to <jats:italic>Borrelia<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Serum samples from well-characterised adult patients with ongoing LB and healthy blood donors were included and investigated using a proximity extension assay (provided by Olink\u00ae) by which 92 different immune response-related human protein biomarkers were analysed simultaneously.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p><jats:bold>In total, 52 LB patients and 75 healthy blood donors were included. The blood donors represented both previously<\/jats:bold> <jats:italic>Borrelia<\/jats:italic> <jats:bold>exposed (n = 34) and not exposed (n = 41) based on anti-<\/jats:bold><jats:italic>Borrelia<\/jats:italic> <jats:bold>antibody status. Ten of the examined 92 proteins differed between patients and blood donors and were chosen for further logistic regression (p&lt;0.1). Six proteins were statistically significantly different between LB patients and blood donors (p&lt;0.05). These six proteins were then combined in an index and analysed using receiver-operating-characteristic curve analysis showing an area under the curve of 0.964 (p&lt;0.001).<\/jats:bold><\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The results from this study suggest that there is an immunological protein pattern that can distinguish a present <jats:italic>Borrelia<\/jats:italic> infection from a previous exposure as well as anti-<jats:italic>Borrelia<\/jats:italic> antibody negative blood donors. Although this method is not adapted for routine clinical use at this point, the possibility is interesting and may open new diagnostic opportunities improving the laboratory diagnostics of LB.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0287586","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T17:25:24Z","timestamp":1687800324000},"page":"e0287586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of potential biomarkers in active Lyme borreliosis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-2496","authenticated-orcid":true,"given":"Ivar","family":"Tjernberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Lager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guro","family":"Furset Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randi","family":"Eikeland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dag","family":"Nyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Brudin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna J.","family":"Henningsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"issue":"2","key":"pone.0287586.ref001","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010\u20132018","volume":"27","author":"KJ Kugeler","year":"2021","journal-title":"Emerg Infect Dis"},{"issue":"3","key":"pone.0287586.ref002","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/femsre\/fux047","article-title":"Lyme borreliosis-from tick bite to diagnosis and treatment","volume":"42","author":"G Stanek","year":"2018","journal-title":"FEMS Microbiol Rev"},{"key":"pone.0287586.ref003","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","author":"AC Steere","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"3","key":"pone.0287586.ref004","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.ttbdis.2018.02.011","article-title":"Subclinical Lyme borreliosis is common in south-eastern Sweden and may be distinguished from Lyme neuroborreliosis by sex, age and specific immune marker patterns","volume":"9","author":"H Carlsson","year":"2018","journal-title":"Ticks Tick Borne Dis"},{"issue":"1","key":"pone.0287586.ref005","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ttbdis.2015.08.009","article-title":"A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and on the Aland Islands, Finland (2008\u20132009)","volume":"7","author":"P Wilhelmsson","year":"2016","journal-title":"Ticks Tick Borne Dis"},{"issue":"4","key":"pone.0287586.ref006","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/10408363.2018.1450353","article-title":"Laboratory diagnosis of Lyme borreliosis: Current state of the art and future perspectives","volume":"55","author":"B Lohr","year":"2018","journal-title":"Crit Rev Clin Lab Sci"},{"issue":"2","key":"pone.0287586.ref007","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cmi.2017.08.025","article-title":"To test or not to test? 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