Antimyelin antibodies and the risk of relapse in patients with a primary demyelinating event
Rauer S, Euler B, Reindl M, Berger T;
Commented by , 23 Jun 2006
Background
Prognostic markers in early MS are important with regard to counseling and individualization of immunomodulatory treatment. A number of clinical characteristics at onset, such as motor, cerebellar and sphincter involvement, progressive course and short inter-attack interval have been related to a poor prognosis, although the reliability on an individual basis is poor.
Paraclinical measurements such as MRI may predict high-risk patients from the number of lesions seen on a baseline scan and a number of potential immune markers have also been described. Among these, interest has focused on serum antibodies against myelin oligodendrocyt glycoprotein (MOG) and myelin basic protein (MBP), which the current study addresses.
Aim
To investigate if the presence of serum MOG and MBP in patients with clinically isolated syndrome (CIS) predict conversion to clinically definite MS (CDMS).
Methods
The authors used sera from 45 patients with CIS and intrathecal IgG synthesis who had presence of IgM antibodies against MOG and MBP. The subjects were selected from a CSF databank and screened retrospectively. CSF, serum and clinical data were collected from the database. Assessment of relapses and time to second demyelinating event was collected from telephone interviews and documented neurological examination.
Antibodies were detected using immunoblot and recombinant MOG (1-125) and human MBP antigen preparations. Fifty-six normal subjects were used as controls.
Results
Twenty-eight (62%) patients developed CDMS during the mean observation period of 60.4 months (range 21-106).
There was no increased risk of developing CDMS in anti-MOG (51%) and anti-MBP (51%) positive patients compared with negative.
Median time span between CIS and CDMS was significantly shorter (p<0.006) for anti-MOG and anti-MBP positive patients (median 5.5 months (range 3-20)) compared with antibody negative patients (median 25.0 months (range 7-43)).
Normal subjects had quite high frequencies of anti-MOG (21%) and anti-MBP (28%) antibodies.
Dr Blinkenberg's comments
The authors could not verify that anti-MOG/MBP predict the risk of a new relapse, and thereby conversion from CIS to CDMS, which was indicated in a former study by Berger et al. (ref. 1). However, median time to the next relapse was significantly shorter in the anti-MOG/MBP positive group, which corroborate results of other studies in this field.
There are a number of methodological considerations that in part may explain the diverging results reported, such as different methods of laboratory measurements, study design and patient selection. Furthermore, data analysis varies among studies and analysis of autoantibody class (IgM or IgG) are also inconsistent, all of which are thoroughly discussed in an editorial commentary (ref. 2).
The current study leaves no clear impression whether anti-MOG/MBP testing could be a useful measurement in a clinical context, although low specificity and predictive value suggest that its role is limited.
The need for reliable paraclinial predictors of disease severity in MS is growing, especially since therapeutic options seem to increase substantially in the near future. In this regard, stratification of patients and individualization of therapy in the early phase of the disease would be optimal, although this seems to be far from reality at the current time.
References
1. Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. New England Journal of Medicine 2003; 349 (2); 139-145
2. Polman CH, Killestein J. Anti-myelin antibodies in multiple sclerosis: clinically useful?. Journal of Neurology, Neurosurgery and Psychiatry 2006; 77; 712