20.500.12556/RUL-144666 Upregulated intrathecal expression of VEGF-A and long lasting global upregulation of proinflammatory immune mediators in vaccine breakthrough tick-borne encephalitis Although anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalescent phase in VBT TBE patients. At the beginning of the neurological phase, VBT patients have significantly higher serum levels of several innate and adaptive inflammatory cytokines compared to healthy donors, reflecting a global inflammatory state. The majority of cytokines, particularly those associated with innate and Th1 responses, are highly concentrated in CSF and positively correlate with intrathecal immune cell counts, demonstrating the localization of Th1 and proinflammatory responses in CNS, the site of disease in TBE. Interestingly, compared to unvaccinated TBE patients, VBT TBE patients have significantly higher CSF levels of VEGF-A and IFN-β and higher systemic levels of neutrophil chemoattractants IL8/CXCL8 and GROα/CXCL1 on admission. Moreover, serum levels of IL-8/CXCL8 and GROα/CXCL1 remain elevated for two months after the onset of neurological symptoms, indicating a prolonged systemic immune activation in VBT patients. These findings provide the first insights into the type of immune responses and their dynamics during TBE in VBT patients. An observed systemic upregulation of neutrophil derived inflammation in acute and convalescent phase of TBE together with highly expressed VEGF-A could contribute to BBB disruption that facilitates the entry of immune cells and supports the intrathecal localization of Th1 responses observed in VBT patients. tick-borne encephalitis vaccine breakthrough cytokines chemokines proinflammatory response VEGF klopni meningoencefalitis cepljenje citokini kemokini vnetni odgovor VEGF true false true Angleški jezik Slovenski jezik Članek v reviji 2023-03-07 13:11:54 2023-03-07 13:11:57 2023-03-08 03:33:18 0000-00-00 00:00:00 2021 0 0 15 str. Vol. 11, art. 696337 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.9 2235-2988 10.3389/fcimb.2021.696337 68801027 fcimb-11-696337.pdf fcimb-11-696337.pdf 1 AA0ABE1EAA762C0057C2E5F4B9B701B7 e8515492b3ac44e20daed8ce1b7f2a93050f4f620be11e891526e4eee9a45a52 a3914d8f-bce1-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167120 https://www.frontiersin.org/articles/10.3389/fcimb.2021.696337/full 1 3cecf113-bce1-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167119 Medicinska fakulteta 0 0 0