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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis
J Kraus1, B S Kuehne, J Tofighi
1Department of Neurology, Research Group for Multiple Sclerosis and Neuroimmunology, Justus-Liebig University Giessen, Giessen, Germany. joerg.r.kraus@neuro.med.uni-giessen.de
Objective:
Chronic and acute dysregulation of the cytokine network has been described in multiple sclerosis (MS). Inflammatory lesions in the central nervous system of MS patients can be assessed by brain magnetic resonance imaging (MRI). This study has been performed to investigate whether changes of cytokines correlate with morphological changes as determined by MRI.
Materials And Methods:
We included 46 patients with relapsing-remitting MS in the study. The serum concentrations of tumor necrosis factor-beta (TNF-beta), TNF receptor-1 (TNFR-1; 55 kDa) and TNFR-2 (75 kDa), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were measured by enzyme linked immunosorbent assay in all patients. Each parameter was correlated with clinical findings and brain MRI parameters. We measured both the number (lesion load) and cumulated area (disease burden) of all lesions on brain MRI. In addition, the number and cumulated area of those lesions showing signs of activity [Gadolinium (Gd)-enhancement, perifocal edema] were determined.
Results:
A non-significant trend (P < 0.05) was found only for the correlation of serum IFN-gamma levels and the number of active MRI lesions showing both Gd-enhancement and perifocal edema in the subgroup of patients (n=21) with active lesions. When corrected for multiple comparisons, this correlation was not significant anymore, as it was above the corrected P-value of 0.001. We could not observe any further correlation of cytokine levels and MRI parameters. However, TNF-beta serum levels were significantly (P < 0.05) elevated in the patient subgroups with higher number of lesions and disease burden, respectively.
Conclusion:
Our data show that the determination of serum levels of the investigated cytokines and cytokine receptors is not useful as a tool to determine subclinical disease activity and severity as assessed by brain MRI.
Insights
Serum cytokine levels do not reliably indicate multiple sclerosis (MS) disease activity or severity. Measuring cytokines like interferon-gamma (IFN-gamma) and tumor necrosis factor-beta (TNF-beta) showed no significant correlation with MRI-detected brain lesions in MS patients.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Radiology
Background:
- Cytokine network dysregulation is implicated in multiple sclerosis (MS).
- Brain magnetic resonance imaging (MRI) assesses central nervous system inflammatory lesions in MS.
Purpose of the Study:
- To investigate the correlation between serum cytokine levels and MRI-assessed morphological changes in MS patients.
- To determine if cytokines can serve as biomarkers for subclinical disease activity and severity in MS.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) measured serum concentrations of TNF-beta, TNFR-1, TNFR-2, IL-4, IL-10, and IFN-gamma in 46 relapsing-remitting MS patients.
- Brain MRI parameters, including lesion load, disease burden, and active lesions (Gd-enhancement, edema), were quantified.
- Cytokine levels were correlated with clinical findings and MRI parameters.
Main Results:
- A non-significant trend was observed between serum IFN-gamma and the number of active MRI lesions in a subgroup of patients.
- This trend lost significance after correction for multiple comparisons.
- Elevated TNF-beta serum levels showed a significant correlation with a higher number of lesions and greater disease burden.
Conclusions:
- Serum levels of the investigated cytokines and receptors are not effective tools for assessing subclinical MS disease activity or severity via MRI.
- Current cytokine measurements lack diagnostic utility for predicting MS progression based on imaging findings.

