Intrathecal activation of the complement system and disability in multiple sclerosis

Area of Science:

• Neuroimmunology
• Complement System Biology

Background:

• Multiple sclerosis (MS) pathogenesis may involve autoimmune processes in the central nervous system.
• Complement system activation is implicated in the disease's development.

Purpose of the Study:

• To investigate complement activation in patients with demyelinating diseases, specifically optic neuritis (ON) and MS.
• To assess the correlation between complement activation markers, demyelination, and neurological disability.

Main Methods:

• Cerebrospinal fluid (CSF) and plasma samples analyzed from 65 patients (MS, ON, controls).
• Complement activation assessed via C3 molecule and terminal complement complex (TCC) levels.
• Demyelination measured by myelin basic protein (MBP) in CSF; disability by Kurtzke EDSS score.

Main Results:

• Initial complement cascade activation observed in all demyelinating disease groups, but not correlated with demyelination or disability.
• Elevated TCC concentrations found in patients experiencing MS attacks beyond ON.
• Significant correlations found between CSF TCC, MBP, and neurological disability, with TCC showing the strongest link to disability (r=0.55).

Conclusions:

• Full complement cascade activation during MS attacks may occur in advanced disease stages.
• Complement activation significantly correlates with neurological disability, particularly in later disease stages.
• Inhibiting complement activation could be a therapeutic strategy to mitigate neurological disability in MS patients.