Intrathecal activation of the complement system and disability in multiple sclerosis.
BACKGROUND
The pathogenesis of multiple sclerosis (MS) appears to involve autoimmune phenomena in the central nervous system. Activation of the complement system is suggested to be involved in the pathogenesis.


METHODS
Cerebrospinal fluid (CSF) and plasma samples from 65 patients with acute optic neuritis (ON) as a possible first symptom of MS (n=18), ON (n=16) or other attacks of clinically definite MS (n=15), and neurological control subjects (n=16) were studied. Activation of the initial part of the complement activation cascade was assessed by measuring activation of the C3 molecule; terminal activation of the complement cascade was assessed by measuring the terminal complement complex (TCC). Demyelination was estimated by the CSF concentration of myelin basic protein and neurological disability was assessed with the Kurtzke expanded disability status scale (EDSS) score.


RESULTS
Activation of the initial part of the complement activation cascade occurred in each of the three groups of patients with demyelinating disease, but was not correlated to demyelination or disability. Increased concentrations of TCC were detected in patients with attacks of MS other than ON. The CSF concentrations of TCC, myelin basic protein (MBP) and neurological disability correlated significantly. The strongest correlation was between neurological disability and the CSF concentration of TCC (r=0.55, P=0.003).


CONCLUSIONS
Full activation of the complement cascade during attacks of MS may be restricted to patients with more advanced disease and is significantly correlated to the degree of neurological disability. This suggests that specific treatment with agents that inhibit complement activation may interfere with mechanisms involved in the pathogenesis of neurological disability in patients with MS.
Sellebjerg
F
F
Department of Neurology, University of Copenhagen, Glostrup Hospital, Denmark.
Jaliashvili
I
I
Christiansen
M
M
Garred
P
P
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D003167:Complement Activation; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000276:immunology / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000503:physiopathology; D009902:Optic Neuritis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000503:physiopathology