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Serial analysis of circulating adhesion molecules and TNF receptor in serum from patients with multiple sclerosis:
P Rieckmann1, S Martin, I Weichselbraun
1Department of Neurology, University of Göttingen, Germany.
Insights
Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) indicate disease activity in multiple sclerosis (MS) patients. Higher circulating tumor necrosis factor receptor p60 (cTNF-R p60) levels are associated with MS remission.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Monitoring disease activity and inflammatory markers is crucial for managing MS.
- Adhesion molecules and cytokine receptors are implicated in MS pathogenesis.
Purpose of the Study:
- To determine serum levels of specific adhesion molecules and a cytokine receptor in relapsing-remitting MS patients.
- To correlate these levels with disease activity, including relapses and MRI-detected progression.
- To identify potential biomarkers for MS disease activity and remission.
Main Methods:
- Serial measurement of serum levels for circulating intercellular adhesion molecule-1 (cICAM-1), circulating endothelial leukocyte adhesion molecule-1 (cELAM-1), circulating L-selectin (cL-selectin), and circulating tumor necrosis factor receptor p60 (cTNF-R p60) in 29 MS patients over 12 months.
- Assessment of disease activity through clinical relapses and MRI-defined new lesions.
- Comparison of marker levels between clinically active and stable MS patients, and at different time points relative to relapses.
Main Results:
- Clinically active MS patients showed significantly higher cumulative cICAM-1 production compared to stable patients (p < 0.001).
- Serum cICAM-1 levels significantly increased at the time of relapse (p < 0.001).
- Higher serum cTNF-R p60 levels were observed in stable MS patients compared to active MS patients (p < 0.005), with peak levels occurring 4 weeks post-relapse (p < 0.01).
- cL-selectin levels were significantly higher in all MS patients compared to healthy donors, while cELAM-1 levels showed no difference.
Conclusions:
- Serum cICAM-1 serves as a valuable indicator of disease activity in relapsing-remitting MS.
- Elevated serum cTNF-R p60 levels are associated with periods of remission in MS.
- These findings highlight distinct inflammatory profiles in MS serum and suggest potential biomarker utility.
Abstract:
We determined the serum levels for circulating adhesion molecules (circulating intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with relapsing-remitting MS serially over a period of 12 months. During this period there were 27 relapses in 14 patients (48%). There was progression of disease activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on nonenhancing, T2-weighted MRIs of the head. Clinically active patients with relapse or disease progression on MRI (n = 18) had frequent fluctuations in their serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There were significant differences in the cumulative cICAM-1 production between the two groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p < 0.005). A significant increase in cICAM-1 levels was present at the time of a relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were significantly higher than in healthy donors, whereas there were no differences for cELAM-1. These results reflect distinct changes of inflammatory variables in serum of patients with MS and revealed that cICAM-1 is an indicator for disease activity and that high serum levels for cTNF-R p60 are associated with remission.