{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T19:50:21Z","timestamp":1767383421489,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Narodowe Centrum Nauki (National Science Centre), Poland","award":["2018\/31\/B\/NZ6\/02744"],"award-info":[{"award-number":["2018\/31\/B\/NZ6\/02744"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathogenesis of the central nervous system (CNS) pathology in tick-borne encephalitis (TBE) remains unclear. We attempted to identify mediators of the blood\u2013brain barrier (BBB) disruption in human TBE in paired serum and cerebrospinal fluid (CSF) samples from 100 TBE patients. CSF albumin quotient (Qalb) was calculated as a measure of BBB impairment. Concentrations of cytokines, cytokine antagonists, adhesion molecules, selectins and matrix metalloproteinases (MMP) were measured with a multiplex bead assay. Single nucleotide polymorphisms (SNP) in genes MIF, TNF, TNFRSF1A, TNFRSF1B, IL-10, TLR3 and TLR4 were studied in patient blood DNA extracts and analyzed for associations with Qalb and\/or cytokine concentrations. The multivariate regression models of Qalb were built with the soluble mediators as independent variables. The best models obtained included L-selectin, P-selectin, sVCAM, MMP7, MMP8 (or MMP9) and IL-28A as positive and IL-12p70, IL-15, IL-6R\u03b1\/IL-6 ratio and TNF-RII\/TNF\u03b1 ratio as negative correlates of Qalb. The genotype did not associate with Qalb, but polymorphism rs4149570 (in TNFRSF1A) associated with TNF\u03b1 and rs1800629 (TNF) with MIF concentration. We confirm the association of the TNF\u03b1-dependent response, L-selectin and MMP8\/MMP9 with BBB disruption and identify its novel correlates (IL-12, IL-15, IL-28A, MMP7). We detect no genotype associations with BBB function in TBE.<\/jats:p>","DOI":"10.3390\/ijms26041503","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:34:32Z","timestamp":1739252072000},"page":"1503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Factors Associated with the Blood\u2013Brain Barrier Dysfunction in Tick-Borne Encephalitis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-3285","authenticated-orcid":false,"given":"Sambor","family":"Grygorczuk","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0072-2180","authenticated-orcid":false,"given":"Piotr","family":"Czupryna","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-602X","authenticated-orcid":false,"given":"Diana","family":"Martonik","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Adamczuk","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Parfieniuk-Kowerda","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6420-5545","authenticated-orcid":false,"given":"Anna","family":"Grzeszczuk","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wioletta","family":"Pawlak-Zalewska","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Dunaj-Ma\u0142yszko","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaja","family":"Mielczak","sequence":"additional","affiliation":[{"name":"Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-1084","authenticated-orcid":false,"given":"Mi\u0142osz","family":"Parczewski","sequence":"additional","affiliation":[{"name":"Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Moniuszko-Malinowska","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Neuroinfections, Medical University in Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.nbd.2009.07.031","article-title":"The blood-brain barrier and immune function and dysfunction","volume":"37","author":"Banks","year":"2010","journal-title":"Neurobiol. 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