Increased serum levels of soluble CD14 indicate stable multiple sclerosis.

The aim of this study was to evaluate a possible role of soluble CD14 (sCD14) in multiple sclerosis (MS). We found that sCD14 serum levels measured by ELISA were higher in MS patients compared to neurological and healthy controls. Within the MS group sCD14 levels were increased in relapsing-remitting and secondary progressive MS compared to primary progressive MS. Furthermore, sCD14 concentrations were increased during stable disease. An increased expression of sCD14 was also detected after treatment with interferon-beta. In summary, we report evidence that serum sCD14 levels are increased in MS and correlate inversely with disease activity in relapsing MS patients.

Daytime sleepiness is not increased in mild to moderate multiple sclerosis: a pupillographic study.

BACKGROUND: Daytime sleepiness has been described in multiple sclerosis (MS); a combination of MS and narcolepsy has also been observed in a few case reports. In this study, we investigated daytime sleepiness in a general sample of MS patients compared to healthy controls with the pupillographic sleepiness test (PST) and the Epworth and Stanford sleepiness scales (ESS, SSS). METHODS: A PST was performed in consecutive MS patients and controls. Additionally, a questionnaire including the ESS and the SSS was applied. RESULTS: Sixty-one MS patients (29 men and 32 women, age 34.5+/-8.3 years, mean disease duration 7.4+/-6.6 years, expanded disability status scale (EDSS) 1.7+/-1.2 (mean +/- sd)) and 42 age-matched controls (13 men and 29 women, age 36.9+/-12.9 years) participated in this study. In the MS group, the pupillary unrest index (PUI) was 5.0+/-2.0, the ESS 7.4+/-3.5 and the SSS 2.4+/-1.2, whereas in the control group, the PUI was 4.7+/-1.8, the ESS 8.4+/-4.0 and the SSS 2.4+/-1.2 (mean +/- sd). These differences were not significant. No correlation was found between PUI and the ESS or the SSS. Furthermore, no correlation was found between EDSS and sleepiness measured by PUI, ESS and SSS. CONCLUSION: In a general sample of MS patients with mild to moderate disease, there was no evidence for overall increased daytime sleepiness compared to healthy controls.

Epitope specificity of neutralizing antibodies against IFN-beta.

Neutralizing antibodies (NAb), a subset of antibodies against interferon-beta (IFN-beta) that inhibit activation of the IFN-beta receptor, are presumed to bind to the receptor-binding site of IFN-beta. The aim of this study was to identify specific epitopes for human NAb and nonneutralizing antibodies (NNAb) on the IFN-beta molecule. Thirty-one 12-mer peptides and one 11-mer peptide representing the amino acid sequence of the human IFN-beta molecule were used as antigens in an ELISA antibody assay. Significant antibody binding was observed at residues 1-12, 121-132, and 151-162. NNAb and NAb recognized residues 121-132 with equal frequency, but NAb had higher titers. NAb bound significantly more frequently to residues 1-12 and 151-162. There was a significant positive correlation between NAb titers and titers against residues 1-12. Binding to residues 1-12 was more pronounced in patients treated with IFN-beta1a than in patients treated with IFN-beta1b. Our results indicate a qualitative and quantitative difference between NAb and NNAb, with special emphasis on the recognition of different epitopes.

Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event.

BACKGROUND: Most patients with multiple sclerosis initially present with a clinically isolated syndrome. Despite the fact that clinically definite multiple sclerosis will develop in up to 80 percent of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated magnetic resonance imaging (MRI). We investigated whether the presence of serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) in patients with a clinically isolated syndrome predicts the interval to conversion to clinically definite multiple sclerosis. METHODS: A total of 103 patients with a clinically isolated syndrome, positive findings on cerebral MRI, and oligoclonal bands in the cerebrospinal fluid were studied. At base line, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified. Neurologic examinations for relapse or disease progression (defined as conversion to clinically definite multiple sclerosis) were performed at base line and subsequently every three months. RESULTS: Patients with anti-MOG and anti-MBP antibodies had relapses more often and earlier than patients without these antibodies. Only 9 of 39 antibody-seronegative patients (23 percent) had a relapse, and the mean (+/-SD) time to relapse was 45.1+/-13.7 months. In contrast, 21 of 22 patients (95 percent) with antibodies against both MOG and MBP had a relapse within a mean of 7.5+/-4.4 months, and 35 of 42 patients (83 percent) with only anti-MOG antibodies had a relapse within 14.6+/-9.6 months (P<0.001 for both comparisons with antibody-seronegative patients). The adjusted hazard ratio for the development of clinically definite multiple sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6) among the patients who were seropositive for both antibodies and 31.6 (95 percent confidence interval, 9.5 to 104.5) among the patients who were seropositive only for anti-MOG antibodies, as compared with the seronegative patients. CONCLUSIONS: Analysis of antibodies against MOG and MBP in patients with a clinically isolated syndrome is a rapid, inexpensive, and precise method for the prediction of early conversion to clinically definite multiple sclerosis. This finding may be important for the counseling and care of patients with a first demyelinating event suggestive of multiple sclerosis.