Selected Biomarkers of Tick-Borne Encephalitis: A Review

Abstract

Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system—most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.

Serum and cerebrospinal fluid phosphorylated neurofilament heavy subunit as a marker of neuroaxonal damage in tick-borne encephalitis

“…In addition, several biomarkers for TBE have been identified in serum or CSF samples (reviewed in [15]), which may be useful for potential application in the diagnosis, prognosis, monitoring, or treatment of TBE [15]. For example, high-mobility group box 1 or chemokine (C-X-C motif) ligand (CXCL) 13 can be used to distinguish TBE meningitis from meningoencephalitis [15][16][17]. The levels of λ-free light chains, matrix metalloproteinase-9, or CXCL1 can be used as indicators of blood-brain barrier disruption [15,18,19].…”

“…For example, high-mobility group box 1 or chemokine (C-X-C motif) ligand (CXCL) 13 can be used to distinguish TBE meningitis from meningoencephalitis [15][16][17]. The levels of λ-free light chains, matrix metalloproteinase-9, or CXCL1 can be used as indicators of blood-brain barrier disruption [15,18,19]. Several other cytokines and chemokines, along with growth factors, monoamine neurotransmitters and other molecules, can be used as biomarkers for TBE [15,[20][21][22][23][24][25][26][27].…”

“…The levels of λ-free light chains, matrix metalloproteinase-9, or CXCL1 can be used as indicators of blood-brain barrier disruption [15,18,19]. Several other cytokines and chemokines, along with growth factors, monoamine neurotransmitters and other molecules, can be used as biomarkers for TBE [15,[20][21][22][23][24][25][26][27].…”

Tick-Borne Encephalitis Virus: A Comprehensive Review of Transmission, Pathogenesis, Epidemiology, Clinical Manifestations, Diagnosis, and Prevention

“…Still, it is important to note that these additional biomarkers only provide supportive evidence and do not independently confirm the diagnosis of TBE. A recent review pinpointed several candidate biomarkers that can be used in the TBE diagnostic, prognostic, and monitoring stages; these include chemokines such as CCL2, CCL7, CXCL1, CXCL2, CXCL9, and CXCL12 [ 196 ].…”

Tick-borne zoonotic flaviviruses and Borrelia infections in wildlife hosts: What have field studies contributed?

“…Recent reviews on tick-borne Borrelia spp. and TBFV have focused on getting information on the biology of infection in vertebrate hosts [ 13 , 14 ], reporting prevalence and clinical cases in human [ 15 , 16 ] and discussing diagnostic methodologies [ 17 , 18 ], the role of non-vector transmissions for TBFV [ 19 , 20 ], or on the importance of modelling TBP regarding climate change [ 21 , 22 ]. Some reviews have focused on wildlife hosts but only at a national or continental scale [ 23 , 24 ], or on reservoirs associated with flaviviruses in general, with little focus on TBFV [ 25 ].…”