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Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: correlation with magnetic
H P Hartung1, K Reiners, J J Archelos
1Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Abstract:
Adhesion molecules are important in T-cell trafficking to sites of inflammation. We determined levels of circulating vascular cell adhesion molecule-1 (VCAM-1), L-selectin, and E-selectin in the serum of 147 patients with definite multiple sclerosis of the remitting-relapsing or secondary progressive type. Soluble VCAM-1 and L-selectin concentrations were increased compared to levels in a large group of control subjects. Levels were highest in patients with gadolinium-enhancing lesions on magnetic resonance imaging (VCAM-1: 1,011 +/- 276 vs 626 +/- 87 ng/ml; L-selectin: 1,130 +/- 272 vs 793 +/- 207 ng/ml [mean +/- standard deviation]; p < 0.0001 vs patients without enhancing lesions). Serum levels of soluble tumor necrosis factor receptor (60 kd) were also raised (2.64 +/- 1.23 vs 2.17 +/- 0.69 ng/ml in subjects with other neurological diseases and 2.1 +/- 0.77 ng/ml in healthy control subjects; p < 0.05). Soluble VCAM-1 and L-selectin levels were correlated to concentrations of soluble tumor necrosis factor receptor. In 13 patients with viral encephalitis, similar observations were made. Raised levels of soluble VCAM-1 and L-selectin probably reflect cytokine-induced endothelial cell and T-lymphocyte/monocyte activation occurring in the process of T-cell migration into the central nervous system. Tumor necrosis factor-alpha may be critically involved.
Insights
Elevated levels of vascular cell adhesion molecule-1 (VCAM-1) and L-selectin indicate increased T-cell activation in multiple sclerosis patients, particularly those with active inflammation shown on MRI scans.
Area of Science:
- Neuroimmunology
- Molecular Medicine
- Biomarker Discovery
Background:
- Adhesion molecules mediate T-cell trafficking to inflammatory sites.
- Understanding these molecules is crucial for diagnosing and managing inflammatory neurological diseases.
Purpose of the Study:
- To investigate serum levels of adhesion molecules and soluble tumor necrosis factor receptor in multiple sclerosis (MS) patients.
- To correlate these levels with disease activity and inflammatory markers.
Main Methods:
- Serum samples from 147 MS patients (remitting-relapsing and secondary progressive) and control groups were analyzed.
- Quantification of soluble vascular cell adhesion molecule-1 (VCAM-1), L-selectin, E-selectin, and soluble tumor necrosis factor receptor (60 kd) using immunoassays.
- Correlation of biomarker levels with MRI findings (gadolinium-enhancing lesions) and other clinical parameters.
Main Results:
- Soluble VCAM-1 and L-selectin levels were significantly elevated in MS patients compared to controls.
- These elevated levels were highest in patients with active, gadolinium-enhancing lesions on MRI.
- Serum levels of soluble tumor necrosis factor receptor (60 kd) were also increased in MS patients and correlated with VCAM-1 and L-selectin levels.
- Similar findings were observed in a small cohort of patients with viral encephalitis.
Conclusions:
- Increased serum VCAM-1 and L-selectin suggest cytokine-induced activation of endothelial cells and leukocytes in MS.
- These molecules may serve as biomarkers for active central nervous system inflammation in MS.
- Tumor necrosis factor-alpha is implicated as a key mediator in this inflammatory process.