{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T15:46:59Z","timestamp":1776008819599,"version":"3.50.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Dutch Ministry of Health, Welfare and Sports"},{"name":"Dutch Ministry of Health, Welfare and Sports"},{"name":"Dutch Ministry of Health, Welfare and Sports"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using<jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>strain B31 and various recombinant antigens, and subsequently, the number of<jats:named-content content-type=\"genus-species\">Borrelia<\/jats:named-content>-specific interferon gamma (IFN-\u03b3)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>B31-specific IFN-\u03b3-secreting T cells\/2.5 \u00d7 10<jats:sup>5<\/jats:sup>PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) (<jats:italic>P<\/jats:italic>= 1.000); however, the median number of<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>B31-specific IFN-\u03b3-secreting T cells\/2.5 \u00d7 10<jats:sup>5<\/jats:sup>PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) (<jats:italic>P<\/jats:italic>\u2264 0.016). We conclude that the<jats:named-content content-type=\"genus-species\">Borrelia<\/jats:named-content>ELISpot assay, measuring the number of<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>B31-specific IFN-\u03b3-secreting T cells\/2.5 \u00d7 10<jats:sup>5<\/jats:sup>PBMCs, correlates with exposure to the<jats:named-content content-type=\"genus-species\">Borrelia<\/jats:named-content>bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis.<\/jats:p>","DOI":"10.1128\/jcm.01695-17","type":"journal-article","created":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T11:25:22Z","timestamp":1516706722000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands"],"prefix":"10.1128","volume":"56","author":[{"given":"T.","family":"van Gorkom","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Diakonessenhuis Hospital, Utrecht, the Netherlands"},{"name":"Laboratory for Infectious Diseases and laboratory Surveillance, Centre for Infectious Diseases Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. U. C.","family":"Sankatsing","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Voet","sequence":"additional","affiliation":[{"name":"Department of Neurology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. M.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. H.","family":"Muilwijk","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Salomons","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. J. M.","family":"Vlaminckx","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. W. J.","family":"Bossink","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. W.","family":"Notermans","sequence":"additional","affiliation":[{"name":"Laboratory for Infectious Diseases and laboratory Surveillance, Centre for Infectious Diseases Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. J. M.","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Kremer","sequence":"additional","affiliation":[{"name":"Laboratory for Infectious Diseases and laboratory Surveillance, Centre for Infectious Diseases Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. F. T.","family":"Thijsen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Diakonessenhuis Hospital, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2014.09.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-016-3105-y"},{"key":"e_1_3_3_4_2","first-page":"665","article-title":"Doubling of the number of cases of tick bites and lyme borreliosis seen by general practitioners in the Netherlands","volume":"148","author":"den Boon S","year":"2004","unstructured":"den Boon S, Schellekens JF, Schouls LM, Suijkerbuijk AW, Docters van Leeuwen B, van Pelt W. 2004. Doubling of the number of cases of tick bites and lyme borreliosis seen by general practitioners in the Netherlands. Ned Tijdschr Geneeskd 148:665\u2013670. (In Dutch.)","journal-title":"Ned Tijdschr Geneeskd"},{"key":"e_1_3_3_5_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\u2013591.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_3_6_2","first-page":"74","article-title":"An estimate of Lyme borreliosis incidence in Western Europe","volume":"39","author":"Sykes RA","year":"2017","unstructured":"Sykes RA, Makiello P. 2017. An estimate of Lyme borreliosis incidence in Western Europe. J Public Health (Oxf) 39:74\u201381.","journal-title":"J Public Health (Oxf)"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2807\/esm.11.12.00667-en"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01509.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.28.3.473-479.1990"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-007-0347-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.3.484-509.2005"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02862.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1468-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.1_Part_1.169"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00341-09"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60103-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-117-4-273"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/314053"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.33549\/physiolres.930372","article-title":"Dynamics of cytokine production in human peripheral blood mononuclear cells stimulated by LPS or infected by Borrelia","volume":"52","author":"Jansk\u00fd L","year":"2003","unstructured":"Jansk\u00fd L, Reymanov\u00e1 P, Kopeck\u00fd J. 2003. Dynamics of cytokine production in human peripheral blood mononuclear cells stimulated by LPS or infected by Borrelia. Physiol Res 52:593\u2013598.","journal-title":"Physiol Res"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.3.593"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.3.1530-1536.2004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00118-5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1995.tb03134.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1995.tb03713.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.9.3620-3623.1996"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.4049\/jimmunol.160.2.1022","article-title":"T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis","volume":"160","author":"Gross DM","year":"1998","unstructured":"Gross DM, Steere AC, Huber BT. 1998. T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis. J Immunol 160:1022\u20131028.","journal-title":"J Immunol"},{"key":"e_1_3_3_27_2","volume-title":"CBO-richtlijn Lymeziekte definitief","author":"RIVM","year":"2013","unstructured":"RIVM. 13 July 2013. CBO-richtlijn Lymeziekte definitief. RIVM, Bilthoven, the Netherlands. http:\/\/www.rivm.nl\/Documenten_en_publicaties\/Algemeen_Actueel\/Nieuwsberichten\/2013\/CBO_richtlijn_Lymeziekte_definitief."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells2030607"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2006.06.008"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2004.01019.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-017-3037-1"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.12.3990-3996.1999"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2006.00139.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300212"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2011.10.017"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-325-7_18"},{"key":"e_1_3_3_37_2","first-page":"151","article-title":"Cellular immune response in Lyme disease: the response to mitogens, live Borrelia burgdorferi, NK cell function and lymphocyte subsets","volume":"263","author":"Dattwyler RJ","year":"1986","unstructured":"Dattwyler RJ, Thomas JA, Benach JL, Golightly MG. 1986. Cellular immune response in Lyme disease: the response to mitogens, live Borrelia burgdorferi, NK cell function and lymphocyte subsets. Zentralbl Bakteriol Mikrobiol Hyg A 263:151\u2013159.","journal-title":"Zentralbl Bakteriol Mikrobiol Hyg A"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1988.tb31842.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874205X01206010104"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02756.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2002.01358.x"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.5.1489"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00840.x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198812013192203"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00011"},{"key":"e_1_3_3_46_2","first-page":"530","article-title":"Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors","volume":"9","author":"Varma TK","year":"2002","unstructured":"Varma TK, Lin CY, Toliver-Kinsky TE, Sherwood ER. 2002. Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors. Clin Diagn Lab Immunol 9:530\u2013543.","journal-title":"Clin Diagn Lab Immunol"},{"key":"e_1_3_3_47_2","first-page":"117","article-title":"Image analysis and data management of ELISPOT assay results","volume":"302","author":"Lehmann PV","year":"2005","unstructured":"Lehmann PV. 2005. Image analysis and data management of ELISPOT assay results. Methods Mol Biol 302:117\u2013132.","journal-title":"Methods Mol Biol"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2016.04.019"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1086\/506936"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells1020153"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-114-4-285"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw112"}],"container-title":["Journal of Clinical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JCM.01695-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JCM.01695-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T17:51:15Z","timestamp":1719769875000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JCM.01695-17"}},"subtitle":[],"editor":[{"given":"Nathan A.","family":"Ledeboer","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1128\/JCM.01695-17"],"URL":"https:\/\/doi.org\/10.1128\/jcm.01695-17","relation":{},"ISSN":["0095-1137","1098-660X"],"issn-type":[{"value":"0095-1137","type":"print"},{"value":"1098-660X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01695-17"}}