The Factors Associated with the Blood-Brain Barrier Dysfunction in Tick-Borne Encephalitis

Area of Science:

• Neuroimmunology
• Infectious Diseases
• Molecular Biology

Background:

• The exact mechanisms behind central nervous system (CNS) pathology in tick-borne encephalitis (TBE) are not fully understood.
• Blood-brain barrier (BBB) integrity is crucial for CNS health, and its disruption is implicated in various neurological disorders.

Purpose of the Study:

• To identify specific mediators contributing to BBB disruption in human TBE.
• To investigate the association between soluble factors, genetic polymorphisms, and BBB impairment in TBE patients.

Main Methods:

• Analysis of paired serum and cerebrospinal fluid (CSF) samples from 100 TBE patients.
• Measurement of cytokines, adhesion molecules, selectins, and matrix metalloproteinases (MMPs) using multiplex bead assays.
• Genotyping for single nucleotide polymorphisms (SNPs) in relevant immune response genes.

Main Results:

• CSF albumin quotient (Qalb) indicated BBB impairment.
• Multivariate regression models identified L-selectin, P-selectin, sVCAM, MMP7, MMP8/MMP9, and IL-28A as positive correlates of BBB disruption.
• IL-12p70, IL-15, IL-6Rα/IL-6 ratio, and TNF-RII/TNFα ratio were negative correlates of BBB impairment.
• Specific SNPs associated with TNFα and MIF concentrations, but not directly with BBB function.

Conclusions:

• Confirmed the role of TNFα-dependent responses, L-selectin, and MMP8/MMP9 in TBE-related BBB disruption.
• Identified novel correlates of BBB disruption, including IL-12, IL-15, IL-28A, and MMP7.
• Found no direct association between studied genotypes and BBB function in TBE.