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Published on: September 21, 2021
GM-CSF is a marker of compartmentalised intrathecal inflammation in multiple sclerosis
S-J Martin1,2, K Brand-Arzamendi1,2, G Saab1
1St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
Background:
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by various immune cells. Several studies have demonstrated an expansion of GM-CSF producing T cells in the blood or CSF of people with MS (pwMS). However, whether this equates to greater concentrations of circulating cytokine remains unknown as quantification is difficult with traditional assays.
Objective:
To determine whether GM-CSF can be quantified and whether GM-CSF levels are elevated in pwMS.
Methods:
We employed Single Molecule Array (Simoa) to measure GM-CSF in both CSF and blood. We then investigated relationships between GM-CSF levels and measures of blood-CSF-barrier integrity.
Results:
GM-CSF was quantifiable in all samples and was significantly higher in the CSF of pwMS compared with controls. No association was found between CSF GM-CSF levels and Q-Albumin - a measure of blood-CSF-barrier integrity. CSF GM-CSF correlated with measures of intrathecal inflammation, and these relationships were greater in primary progressive MS compared with relapsing-remitting MS.
Conclusion:
GM-CSF levels are elevated specifically in the CSF of pwMS. Our results suggest that elevated cytokine levels may reflect (at least partial) intrathecal production, as opposed to simple diffusion across a dysfunctional blood-CSF-barrier.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is elevated in the cerebrospinal fluid of people with multiple sclerosis (MS). This suggests intrathecal production rather than diffusion across the blood-brain barrier in MS patients.
Area of Science:
- Neuroimmunology
- Cytokine Signaling
- Multiple Sclerosis Pathogenesis
Background:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine implicated in immune responses.
- Expanded GM-CSF producing T cells are observed in multiple sclerosis (MS) patients.
- Quantifying GM-CSF in biological fluids like CSF and blood presents challenges with traditional assays.
Purpose of the Study:
- To determine if GM-CSF can be reliably quantified in the cerebrospinal fluid (CSF) and blood of people with MS (pwMS).
- To investigate whether GM-CSF levels are elevated in pwMS compared to healthy controls.
- To explore the relationship between GM-CSF levels and blood-CSF-barrier integrity in MS.
Main Methods:
- Utilized Single Molecule Array (Simoa) technology for precise GM-CSF quantification in CSF and blood.
- Compared GM-CSF concentrations between pwMS and control groups.
- Assessed correlations between CSF GM-CSF levels and markers of blood-CSF-barrier function (e.g., Q-Albumin).
Main Results:
- GM-CSF was successfully quantified in all analyzed samples.
- Significantly higher GM-CSF levels were detected in the CSF of pwMS compared to controls.
- No correlation was found between CSF GM-CSF and Q-Albumin, indicating no direct link to blood-CSF-barrier integrity.
- CSF GM-CSF levels correlated with markers of intrathecal inflammation, particularly in primary progressive MS.
Conclusions:
- GM-CSF is elevated specifically within the CSF of individuals with MS.
- The elevated CSF GM-CSF suggests local intrathecal production rather than passive diffusion across a compromised blood-CSF-barrier.
- These findings contribute to understanding the inflammatory mechanisms in MS pathogenesis.
Related Concept Videos
01:21Cerebrospinal Fluid
CSF Production
CSF is produced mainly in the choroid plexus, a network of capillaries and ependymal cells located within the ventricular system of the brain.
01:19Multiple Sclerosis l: Introduction