{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:49:55Z","timestamp":1787060995696,"version":"build-2736575974"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T00:00:00Z","timestamp":1474416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T00:00:00Z","timestamp":1474416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>At present, diagnosis for neurosyphilis remains a major clinical challenge. Venereal Disease Research Laboratory (VDRL) titer of the cerebrospinal fluid (CSF) is suboptimally sensitive to diagnose neurosyphilis, which can be negative in neurosyphilis patients, especially in asymptomatic neurosyphilis patients. In the search for biomarkers of neurosyphilis, we investigated the chemokine profile in CSF of neurosyphilis patients and found that the concentrations of CXCL13, CXCL10 and CXCL8 were selectively elevated in neurosyphilis patients and correlated with CSF protein concentration and CSF-VDRL titer. After antibiotic treatment, the concentration of these chemokines was dramatically reduced. The area under the ROC curve (AUC) of CSF CXCL13, CXCL8,CXCL10 and the CSF\/serum ratio of CXCL13, CXCL8,CXCL10 in the diagnosis of neurosyphilis were 0.940, 0.899, 0.915, 0.963, 0.846 and 0.926, respectively. The corresponding sensitivities\/specificities of CSF CXCL13, CXCL8,CXCL10 and the CSF\/serum ratio of CXCL13, CXCL8,CXCL10 in diagnosis of neurosyphilis were 85.4%\/89.1%, 79%\/90.1% and 79.6%\/91.1%, 86.6%\/99%, 79%\/73.3% and 86%\/92.1%, respectively. Our results suggest that the elevated concentrations of CXCL13, CXCL8, and CXCL10 or their increasing CSF\/serum ratios may be potential biomarkers of neurosyphilis, particularly for asymptomatic neurosyphilis. Reduced concentration of these chemokines may indicate the prognosis of antibiotic therapy.<\/jats:p>","DOI":"10.1038\/srep33569","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T06:46:20Z","timestamp":1474440380000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["CXCL13, CXCL10 and CXCL8 as Potential Biomarkers for the Diagnosis of Neurosyphilis Patients"],"prefix":"10.1038","volume":"6","author":[{"given":"Cuini","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,21]]},"reference":[{"key":"BFsrep33569_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1159\/000350059","volume":"47","author":"F Friedrich","year":"2014","unstructured":"Friedrich, F. et al. Psychosis in neurosyphilis-clinical aspects and implications. Psychopathology 47, 3\u20139 (2014).","journal-title":"Psychopathology"},{"key":"BFsrep33569_CR2","unstructured":"Chinese Center for Disease Prevention and Control; Center for STI and AIDS Prevention and Control (2015)."},{"key":"BFsrep33569_CR3","doi-asserted-by":"publisher","first-page":"855","DOI":"10.7326\/0003-4819-109-11-855","volume":"109","author":"SA Lukehart","year":"1988","unstructured":"Lukehart, S. A. et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Annals of internal medicine 109, 855\u2013862 (1988).","journal-title":"Annals of internal medicine"},{"key":"BFsrep33569_CR4","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1097\/OLQ.0b013e3181f07e91","volume":"38","author":"S Mishra","year":"2011","unstructured":"Mishra, S. et al. The laboratory impact of changing syphilis screening from the rapid-plasma reagin to a treponemal enzyme immunoassay: A case-study from the Greater Toronto Area. Sexually transmitted diseases 38, 190\u2013196 (2011).","journal-title":"Sexually transmitted diseases"},{"key":"BFsrep33569_CR5","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/B978-0-7020-4088-7.00098-5","volume":"121","author":"JR Berger","year":"2013","unstructured":"Berger, J. R. & Dean, D. Neurosyphilis. Handbook of clinical neurology 121, 1461\u20131472 (2013).","journal-title":"Handbook of clinical neurology"},{"key":"BFsrep33569_CR6","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1128\/JCM.00084-11","volume":"49","author":"N Van Burgel","year":"2011","unstructured":"Van Burgel, N., Bakels, F., Kroes, A. & van Dam, A. Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid. Journal of clinical microbiology 49, 2027\u20132030 (2011).","journal-title":"Journal of clinical microbiology"},{"key":"BFsrep33569_CR7","doi-asserted-by":"publisher","first-page":"e48370","DOI":"10.1371\/journal.pone.0048370","volume":"7","author":"B Bielekova","year":"2012","unstructured":"Bielekova, B., Komori, M., Xu, Q., Reich, D. S. & Wu, T. Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation. PloS one 7, e48370, 10.1371\/journal.pone.0048370 (2012).","journal-title":"PloS one"},{"key":"BFsrep33569_CR8","doi-asserted-by":"publisher","first-page":"e0122000","DOI":"10.1371\/journal.pone.0122000","volume":"10","author":"F Shimizu","year":"2015","unstructured":"Shimizu, F. et al. Markedly Increased IP-10 Production by Blood-Brain Barrier in Neuromyelitis Optica. PloS one 10, e0122000, 10.1371\/journal.pone.0122000 (2015).","journal-title":"PloS one"},{"key":"BFsrep33569_CR9","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1212\/WNL.0b013e318211c39a","volume":"76","author":"C Schmidt","year":"2011","unstructured":"Schmidt, C. et al. A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology 76, 1051\u20131058 (2011).","journal-title":"Neurology"},{"key":"BFsrep33569_CR10","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1186\/1471-2334-12-344","volume":"12","author":"JP Borde","year":"2012","unstructured":"Borde, J. P. et al. CXCL13 may improve diagnosis in early neuroborreliosis with atypical laboratory findings. BMC infectious diseases 12, 344 (2012).","journal-title":"BMC infectious diseases"},{"key":"BFsrep33569_CR11","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1128\/JCM.02917-14","volume":"53","author":"KM Mothapo","year":"2015","unstructured":"Mothapo, K. M. et al. Has CXCL13 an Added Value in Diagnosis of Neurosyphilis? Journal of clinical microbiology 53, 1693\u20131696 (2015).","journal-title":"Journal of clinical microbiology"},{"key":"BFsrep33569_CR12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/OLQ.0b013e3181d877a1","volume":"37","author":"CM Marra","year":"2010","unstructured":"Marra, C. M., Tantalo, L. C., Sahi, S. K., Maxwell, C. L. & Lukehart, S. A. CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis. Sexually transmitted diseases 37, 283\u2013287 (2010).","journal-title":"Sexually transmitted diseases"},{"key":"BFsrep33569_CR13","doi-asserted-by":"crossref","unstructured":"Hu, R. et al. Value of CXCL13 in diagnosing asymptomatic neurosyphilis in HIV-infected patients. International journal of STD & AIDS 0956462415577229 (2015).","DOI":"10.1177\/0956462415577229"},{"key":"BFsrep33569_CR14","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1002\/1521-4141(200105)31:5<1544::AID-IMMU1544>3.0.CO;2-I","volume":"31","author":"JL Vissers","year":"2001","unstructured":"Vissers, J. L., Hartgers, F. C., Lindhout, E., Figdor, C. G. & Adema, G. J. BLC (CXCL13) is expressed by different dendritic cell subsets in vitro and in vivo. European journal of immunology 31, 1544\u20131549 (2001).","journal-title":"European journal of immunology"},{"key":"BFsrep33569_CR15","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1182\/blood-2004-02-0701","volume":"104","author":"HS Carlsen","year":"2004","unstructured":"Carlsen, H. S., Baekkevold, E. S., Morton, H. C., Haraldsen, G. & Brandtzaeg, P. Monocyte-like and mature macrophages produce CXCL13 (B cell\u2013attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis. Blood 104, 3021\u20133027 (2004).","journal-title":"Blood"},{"key":"BFsrep33569_CR16","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.ajo.2005.02.026","volume":"140","author":"KM Falkenhagen","year":"2005","unstructured":"Falkenhagen, K. M., Braziel, R. M., Fraunfelder, F. W. & Smith, J. R. B-Cells in ocular adnexal lymphoproliferative lesions express B-cell attracting chemokine 1 (CXCL13). American journal of ophthalmology 140, 335\u2013337 (2005).","journal-title":"American journal of ophthalmology"},{"key":"BFsrep33569_CR17","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.1128\/IAI.01642-06","volume":"75","author":"TA Rupprecht","year":"2007","unstructured":"Rupprecht, T. A. et al. Borrelia garinii induces CXCL13 production in human monocytes through Toll-like receptor 2. Infection and immunity 75, 4351\u20134356 (2007).","journal-title":"Infection and immunity"},{"key":"BFsrep33569_CR18","doi-asserted-by":"publisher","first-page":"527","DOI":"10.3390\/antibiotics3040527","volume":"3","author":"GO Holdren","year":"2014","unstructured":"Holdren, G. O. et al. Antimicrobial Activity of Chemokine CXCL10 for Dermal and Oral Microorganisms. Antibiotics 3, 527\u2013539 (2014).","journal-title":"Antibiotics"},{"key":"BFsrep33569_CR19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/1742-2094-11-79","volume":"11","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10. Journal of neuroinflammation 11, 79 (2014).","journal-title":"Journal of neuroinflammation"},{"key":"BFsrep33569_CR20","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1177\/1352458514537365","volume":"20","author":"S Rossi","year":"2014","unstructured":"Rossi, S. et al. Interleukin-8 is associated with acute and persistent dysfunction after optic neuritis. Multiple Sclerosis Journal 20, 1841\u20131850 (2014).","journal-title":"Multiple Sclerosis Journal"},{"key":"BFsrep33569_CR21","first-page":"1","volume":"8","author":"AJ Henningsson","year":"2011","unstructured":"Henningsson, A. J., Tjernberg, I., Malmvall, B.-E., Forsberg, P. & Ernerudh, J. Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study. Journal of neuroinflammation 8, 1\u201311 (2011).","journal-title":"a large retrospective study"},{"key":"BFsrep33569_CR22","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.jneuroim.2005.03.005","volume":"163","author":"S\u017d Lepej","year":"2005","unstructured":"Lepej, S. \u017d. et al. Increased expression of CXCR3 and CCR5 on memory CD4+ T-cells migrating into the cerebrospinal fluid of patients with neuroborreliosis: the role of CXCL10 and CXCL11. Journal of neuroimmunology 163, 128\u2013134 (2005).","journal-title":"Journal of neuroimmunology"},{"key":"BFsrep33569_CR23","doi-asserted-by":"publisher","first-page":"4740","DOI":"10.1182\/blood-2013-01-476333","volume":"121","author":"JL Rubenstein","year":"2013","unstructured":"Rubenstein, J. L. et al. CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 121, 4740\u20134748 (2013).","journal-title":"Blood"},{"key":"BFsrep33569_CR24","doi-asserted-by":"publisher","first-page":"e3004","DOI":"10.1371\/journal.pntd.0003004","volume":"8","author":"C Wang","year":"2014","unstructured":"Wang, C. et al. Increased interleukin-17 in peripheral blood and cerebrospinal fluid of neurosyphilis patients. PLoS neglected tropical diseases 8, e3004, 10.1371\/journal.pntd.0003004 (2014).","journal-title":"PLoS neglected tropical diseases"},{"key":"BFsrep33569_CR25","doi-asserted-by":"publisher","first-page":"e2528","DOI":"10.1371\/journal.pntd.0002528","volume":"7","author":"K Li","year":"2013","unstructured":"Li, K. et al. Regulatory T cells in peripheral blood and cerebrospinal fluid of syphilis patients with and without neurological involvement. PLoS neglected tropical diseases 7, e2528, 10.1371\/journal.pntd.0002528 (2013).","journal-title":"PLoS neglected tropical diseases"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep33569.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep33569","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep33569.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:32:12Z","timestamp":1672882332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep33569"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,21]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,16]]}},"alternative-id":["BFsrep33569"],"URL":"https:\/\/doi.org\/10.1038\/srep33569","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,21]]},"assertion":[{"value":"22 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33569"}}