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Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
Multifocal motor neuropathy is not associated with altered innate immune responses to endotoxin
Jeroen W Bos1, Ewout J N Groen1, Kevin Budding2
1Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
Objective:
Antibody- and complement-mediated peripheral nerve inflammation are central in the pathogenesis of MMN. Here, we studied innate immune responses to endotoxin in patients with MMN and controls to further our understanding of MMN risk factors and disease modifiers.
Methods:
We stimulated whole blood of 52 patients with MMN and 24 controls with endotoxin and collected plasma. With a multiplex assay, we determined levels of the immunoregulating proteins IL-1RA, IL-1β, IL-6, IL-10, IL-21, TNF-α, IL-8 and CD40L in unstimulated and LPS-stimulated plasma. We compared baseline and stimulated protein levels between patients and controls and correlated concentrations to clinical parameters.
Results:
Protein level changes after stimulation were comparable between groups (p > 0.05). IL-1RA, IL-1β, IL-6 and IL-21 baseline concentrations showed a positive correlation with monthly IVIg dosage (all corrected p-values < 0.016). Patients with anti-GM1 IgM antibodies showed a more pronounced IL-21 increase after stimulation (p 0.048).
Conclusions:
Altered endotoxin-induced innate immune responses are unlikely to be a susceptibility factor for MMN.
Insights
Innate immune responses to endotoxin do not appear to be a risk factor for Multifocal Motor Neuropathy (MMN). Baseline protein levels, however, correlated with intravenous immunoglobulin (IVIg) dosage in MMN patients.
Area of Science:
- Immunology
- Neurology
Background:
- Multifocal Motor Neuropathy (MMN) pathogenesis involves antibody- and complement-mediated peripheral nerve inflammation.
- Understanding innate immune responses to endotoxin may reveal MMN risk factors and disease modifiers.
Purpose of the Study:
- To investigate innate immune responses to endotoxin in MMN patients and controls.
- To identify potential risk factors and disease modifiers in MMN.
Main Methods:
- Whole blood from 52 MMN patients and 24 controls was stimulated with endotoxin (lipopolysaccharide, LPS).
- Plasma levels of key immunoregulating proteins (IL-1RA, IL-1β, IL-6, IL-10, IL-21, TNF-α, IL-8, CD40L) were measured using a multiplex assay.
- Baseline and stimulated protein levels were compared between groups and correlated with clinical parameters.
Main Results:
- Endotoxin stimulation resulted in comparable protein level changes between MMN patients and controls.
- Baseline concentrations of IL-1RA, IL-1β, IL-6, and IL-21 positively correlated with monthly intravenous immunoglobulin (IVIg) dosage.
- Patients with anti-GM1 IgM antibodies exhibited a more pronounced increase in IL-21 after stimulation.
Conclusions:
- Altered endotoxin-induced innate immune responses are unlikely to be a susceptibility factor for MMN.
- Specific baseline protein levels may be associated with IVIg treatment intensity in MMN.
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