Matrix metalloproteinase-9 is increased and correlates with severity in Guillain-Barré syndrome

• Published in: Neurology Vol. 53; no. 8; pp. 1683 - 1691
• Main Authors: CREANGE, A, SHARSHAR, T, PLANCHENAULT, T, CHRISTOV, C, PORON, F, RAPHAËL, J.-C, GHERARDI, R. K
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 10-11-1999
• Subjects: Biological and medical sciences; Biopsy; Cells, Cultured; Guillain-Barre Syndrome - enzymology; Guillain-Barre Syndrome - pathology; Guillain-Barre Syndrome - physiopathology; Humans; Immunohistochemistry; Lymphocytes - enzymology; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 3 - blood; Matrix Metalloproteinase 9 - blood; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Peroneal Nerve - pathology; Prospective Studies; Severity of Illness Index; Tissue Inhibitor of Metalloproteinase-1 - blood; Human; Nervous system diseases; Enzyme; Immunocytochemistry; Exploration; Gene expression; Inflammatory disease; Pathology; Peptidases; Hydrolases; Peripheral nerve disease; ELISA assay; Guillain Barré syndrome
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.53.8.1683

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).
MMPs are able to proteolysis of basement membranes and other matrix components, promoting transmigration of inflammatory cells from circulation to nerve tissue.
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.
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.
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.