Is peripheral immunity regulated by blood-brain barrier permeability changes?

Area of Science:

• Neuroimmunology
• Autoimmunity
• Blood-Brain Barrier Research

Background:

• S100B protein is a marker of blood-brain barrier (BBB) integrity, appearing in circulation upon BBB breach.
• Elevated S100B levels correlate with clinical indicators of BBB disruption (BBBD).
• Repeated insults can lead to S100B autoantibody production.

Purpose of the Study:

• To investigate if S100B in extracranial tissues results from peripheral uptake by antigen-presenting cells.
• To determine if this uptake induces autoantibodies against S100B.
• To explore the link between BBBD and systemic immune responses.

Main Methods:

• Utilized animal models of seizures and patients with repeated BBBD.
• Employed immunohistochemistry, RNA analysis, tracer injection, and serum analysis.
• Detected S100B protein in immune cells and BBB endothelium; quantified uptake by dendritic cells.

Main Results:

• S100B protein was found in immune cells of spleen, thymus, lymph nodes, and resident immune cells, as well as BBB endothelium.
• Uptake of labeled S100B by splenic dendritic cells was increased during status epilepticus and BBBD.
• A surge in serum S100B preceded seizures, and patients with therapeutic BBBD showed autoimmune responses against S100B.

Conclusions:

• S100B protein can be taken up by peripheral immune cells, potentially triggering autoimmune responses.
• BBBD may integrate central nervous system events with systemic immunity via S100B and immune cell activation.
• Extravasated S100B could initiate a pathological autoimmune reaction linking systemic and CNS immunity.