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Matrix metalloproteinase-9 is increased and correlates with severity in Guillain-Barré syndrome
A Créange1, T Sharshar, T Planchenault
1Réseau de Neuroimmunologie de Nerf Périphérique (AP/HP), The Groupe d'Etudes et de Recherches sur le Muscle et le Nerf, GERMEN, EA2341 Université Paris 12, Val-de-Merne, France.
Objective:
To study the expression and activity of matrix metalloproteinases (MMPs) MMP-2 (72-kd type IV collagenase, gelatinase A), MMP-3 (58-kd stromelysin-1), and MMP-9 (92-kd type IV collagenase, gelatinase B) and tissue inhibitors of MPs (TIMP) in patients with Guillain-Barre syndrome (GBS).
Background:
MMPs are able to proteolysis of basement membranes and other matrix components, promoting transmigration of inflammatory cells from circulation to nerve tissue.
Methods:
Twenty-five patients with GBS were analyzed according to the phase of the disease, i.e., progression, plateau, early recovery, and late recovery. Determinations of MMP-2, MMP-3, MMP-9, and TIMP-1 were performed using ELISA, zymography, and immunocytochemistry in circulation or peripheral nerve.
Results:
MMP-9 plasma levels were increased in 67% of patients on admission and decreased from progression to late recovery (p < 0.002). During the course of GBS, MMP-9 was progressively balanced by its inhibitor TIMP-1, as assessed by the MMP-9/TIMP-1 ratio. MMP-9 and TIMP-1 plasma levels and the MMP-9/TIMP-1 ratio correlated positively with disability. MMP-2 expression was similar to controls. MMP-3 activity was not detected, and plasma levels were not different from those in controls. Positive MMP-9 immunolabeling was 51 +/- 11% of circulating lymphocytes. It was observed in some endothelial cells and mononuclear cells adherent to the endothelium and close to myelinated fibers.
Conclusions:
Circulating matrix metalloproteinases (MMP-9) correlates with disease severity in Guillain-Barré syndrome (GBS). MMP-9 likely represents an important molecule in the pathogenesis of GBS and therefore could represent an interesting therapeutic target.
Insights
Matrix metalloproteinase-9 (MMP-9) levels correlate with disease severity in Guillain-Barré syndrome (GBS). This finding suggests MMP-9 is important in GBS pathogenesis and may be a therapeutic target.
Area of Science:
- Neuroimmunology
- Biochemistry
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) degrade basement membranes, facilitating inflammatory cell migration into nerve tissue.
- MMPs play a role in inflammatory and autoimmune neurological conditions.
Purpose of the Study:
- To investigate the expression and activity of MMP-2, MMP-3, MMP-9, and TIMP-1 in patients with Guillain-Barré syndrome (GBS).
- To correlate MMP and TIMP levels with disease severity and phase in GBS.
Main Methods:
- Analysis of 25 GBS patients across disease phases (progression, plateau, recovery).
- Quantification of MMP-2, MMP-3, MMP-9, and TIMP-1 using ELISA, zymography, and immunocytochemistry.
- Assessment of MMP-9/TIMP-1 ratio to evaluate inhibitor balance.
Main Results:
- Elevated MMP-9 plasma levels were observed in 67% of GBS patients on admission, decreasing during recovery.
- The MMP-9/TIMP-1 ratio positively correlated with GBS disability.
- MMP-9 was detected on circulating lymphocytes, endothelial cells, and mononuclear cells near nerve fibers.
Conclusions:
- Circulating MMP-9 levels are significantly associated with disease severity in GBS.
- MMP-9 is implicated in the pathogenesis of GBS.
- MMP-9 represents a potential therapeutic target for GBS management.