Serum matrix metalloproteinase-9 (MMP-9) as a biomarker in paediatric and adult tick-borne encephalitis patients

Virus Res. 2023 Jan 15:324:199020. doi: 10.1016/j.virusres.2022.199020. Epub 2022 Dec 15.


Matrix metalloproteinases (MMPs) play an important role in central nervous system infections. We analysed the levels of 8 different MMPs in the cerebrospinal fluid (CSF) of 89 adult patients infected with tick-borne encephalitis (TBE) virus and compared them with the levels in a control group. MMP-9 was the only MMP that showed significantly increased CSF levels in TBE patients. Serum MMP-9 levels were subsequently measured in 101 adult TBE patients at various time points during the neurological phase of TBE and at follow-up. In addition, serum MMP-9 was analysed in 37 paediatric TBE patients. Compared with control levels, both paediatric and adult TBE patients had significantly elevated serum MMP-9 levels. In most adult patients, serum MMP-9 levels peaked at hospital admission, with higher serum MMP-9 levels observed in patients with encephalitis than in patients with meningitis. Elevated serum MMP-9 levels were observed throughout hospitalisation but decreased to normal levels at follow-up. Serum MMP-9 levels correlated with clinical course, especially in patients heterozygous for the single-nucleotide polymorphism rs17576 (A/G; Gln279Arg) in the MMP9 gene. The results highlight the importance of MMP-9 in the pathogenesis of TBE and suggest that serum MMP-9 may serve as a promising bioindicator of TBE in both paediatric and adult TBE patients.

Keywords: Cerebrospinal fluid; Matrix matalloproteinase; Neuroinfection; Tick-borne encephalitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Child
  • Encephalitis Viruses, Tick-Borne* / genetics
  • Encephalitis, Tick-Borne* / cerebrospinal fluid
  • Encephalitis, Tick-Borne* / diagnosis
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Polymorphism, Single Nucleotide


  • Biomarkers
  • Matrix Metalloproteinase 9
  • MMP9 protein, human