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Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis using QuantiFERON Monitor
Zbysek Pavelek1, Ondrej Soucek2, Jan Krejsek2
1Department of Neurology, Faculty of Medicine and University Hospital Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
Insights
Interferon-gamma (IFN-γ) levels were lower in multiple sclerosis (MS) patients compared to healthy controls, indicating reduced immune activation. Fingolimod treatment further suppressed IFN-γ production in MS patients.
Area of Science:
- Immunology
- Neuroscience
Background:
- The QuantiFERON®-Monitor (QFM) assay measures interferon-gamma (IFN-γ) production as a marker of immune response.
- Multiple Sclerosis (MS) involves complex immune dysregulation.
- This study investigates IFN-γ levels in different MS patient groups and healthy controls.
Purpose of the Study:
- To evaluate the QuantiFERON®-Monitor (QFM) test's utility in assessing immune status in multiple sclerosis (MS).
- To compare IFN-γ levels between healthy controls (HC), pharmacologically untreated secondary progressive MS (pMS), and fingolimod-treated relapsing-remitting MS (fMS) patients.
- To test the hypothesis that lower IFN-γ levels correlate with immunosuppression.
Main Methods:
- An observational study involving 86 HC, 96 pMS patients, and 78 fMS patients.
- Whole blood samples were collected and stimulated within 8 hours.
- Plasmatic IFN-γ levels were quantified using the QFM assay and ELISA.
Main Results:
- Healthy controls exhibited significantly higher median IFN-γ levels (228.00 IU/ml) compared to both pMS (144.80 IU/ml) and fMS (130.50 IU/ml) groups.
- Statistical significance was observed between HC and pMS (P=0.0071) and between HC and fMS (P=0.0468).
- Validation analyses confirmed these findings, excluding the impact of disease duration and disability scores.
Conclusions:
- MS patients demonstrate a reduced capacity for immune system activation compared to healthy individuals.
- Fingolimod treatment effectively suppresses IFN-γ production in MS patients.
- Lower baseline QFM scores in MS patients may suggest a fundamental immune system dysfunction.
Background:
The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function.
Methods:
This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml.
Results:
The results showed that controls had nearly 2-fold higher levels of IFN-γ (QFM score) in median (q25, q75) 228.00 (112.20, 358.67) than the MS patient groups: pMS 144.80 (31.23, 302.00); fMS 130.50 (39.95, 217.07) which is statistically significant difference P-value: HC vs. pMS = 0.0071; HC vs. fMS = 0.0468. This result was also confirmed by a validation analysis to exclude impact of variable factors, such as disease duration and Expanded Disability Status Scale scores.
Conclusions:
Results showed that controls had higher levels of IFN-γ production than the MS patient groups and suggest that MS patients included in this study have a lower ability of immune system activation than HC. Results confirm that fingolimod is able to suppress production of IFN-γ. The fact that the QFM score of MS patients is significantly lower than that of HC may indicate a dysfunctional state of the immune system in baseline conditions.
