Oligoclonal restriction of antiviral immunoreaction in oligoclonal band-negative MS patients.
OBJECTIVE
Presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a diagnostic hallmark of multiple sclerosis (MS). However, up to 10% of patients were OCB negative in routine laboratory tests. The aim of this study was to determine whether there is at least an oligoclonal restriction of intrathecal antibody synthesis against measles, rubella and/or varicella zoster virus (MRZ-specific OCB) in CSF from oligoclonal bands-negative patients with MS.


METHODS
CSF and serum samples from 17 well-defined OCB-negative patients with MS were analysed for MRZ-specific OCB. We performed isoelectric focusing (IEF) combined with affinity blotting using viral antigens, detection with a highly sensitive chemiluminescence technique and recording with X-ray films. Controls included 18 OCB-positive patients with MS and 11 patients with pseudotumor cerebri (PTC).


RESULTS
Exclusive or predominant MRZ-specific OCB in CSF against at least one virus species were present in 8 of 17 patients with MS (47.1%; P = 0.0422), suggesting an oligoclonal intrathecal immune response, although OCB of total IgG were absent. Only a very weak oligoclonal reaction against varicella zoster virus in CSF from one of the PTC controls was detectable. Thirteen of 18 (72.2%; P = 0.0013) OCB-positive patients with MS showed also MRZ-specific oligoclonal bands against at least 1 neurotropic virus in CSF.


CONCLUSIONS
MRZ-specific OCB argue for existence of a chronic intrathecal immune reaction also in routine laboratory-OCB-negative patients with MS. This phenomenon reflects oligoclonal restriction of the humoral immunoreaction as well as polyspecific intrathecal antibody synthesis, which are both characteristics in the chronic inflammatory process of MS.
Department of Neurology, Albert Ludwigs University, Freiburg, Germany.
O
O
Stich
J
J
Kluge
J
J
Speck
S
S
Rauer
D000328:Adult; D000914:Antibodies, Viral / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*; D012409:Rubella / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D043025:Oligoclonal Bands
absence of oligoclonal bands; measles, rubella and/or varicella zoster virus reaction; multiple sclerosis; specific intrathecal antibody synthesis; specific oligoclonal bands