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Increased serum levels of soluble CD95 (APO-1/Fas) in relapsing-remitting multiple sclerosis
F Zipp1, M Weller, P A Calabresi
1Department of Neurology, University of Tübingen, Germany.
Insights
Serum soluble CD95 levels are elevated in multiple sclerosis patients and correlate with disease progression. High CD95 levels predict neutralizing antibody formation to interferon-beta treatment.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- CD95/CD95 ligand interactions regulate T-cell responses.
- Soluble CD95 (sCD95) role in neurological diseases is under investigation.
Purpose of the Study:
- To investigate serum sCD95 levels in patients with relapsing remitting multiple sclerosis (RRMS).
- To explore the relationship between sCD95 levels, clinical disability, and MRI findings.
- To assess the impact of interferon-beta (IFNbeta) treatment on sCD95 levels and its association with treatment response.
Main Methods:
- Serum sCD95 levels were measured in RRMS patients.
- Cross-sectional and longitudinal analyses were performed correlating sCD95 with clinical data (Expanded Disability Status Scale) and MRI.
- sCD95 levels were monitored during IFNbeta treatment, and associations with neutralizing antibody formation were analyzed.
Main Results:
- Serum sCD95 levels were significantly elevated in RRMS patients compared to controls.
- sCD95 levels did not correlate with clinical disability or MRI lesions in cross-sectional analysis.
- Longitudinal analysis revealed an association between increased Expanded Disability Status Scale scores and high sCD95 levels.
- IFNbeta treatment induced transient changes in sCD95 levels.
- Patients developing neutralizing antibodies to IFNbeta had higher baseline sCD95 levels.
Conclusions:
- Elevated serum sCD95 is a feature of RRMS.
- sCD95 levels may serve as a biomarker for disease activity and progression in RRMS.
- Baseline sCD95 levels could predict the development of neutralizing antibodies to IFNbeta treatment in RRMS patients.
Abstract:
CD95/CD95 ligand interactions are critically involved in the negative regulation of peripheral T-cell responses. Here, we report that serum levels of soluble CD95 are significantly elevated in patients with relapsing remitting multiple sclerosis. In a transectional study, CD95 levels did not correlate with clinical disability or lesion formation on magnetic resonance imaging. Longitudinally, Expanded Disability Status Scale changes were associated with high CD95 levels. Interferon-beta (IFNbeta) treatment led to an initial increase and subsequent decline of serum CD95 levels. Interestingly, patients generating neutralizing antibodies to the drug had significantly higher baseline CD95 levels before IFNbeta treatment than those without neutralizing antibodies.