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

From the Réseau de Neuroimmunologie du Nerf Périphérique (AP/HP) (Drs. Créange, Sharshar, Raphaël, and Gherardi), the Groupe d’Etudes et de Recherches sur le Muscle et le Nerf (Drs. Créange, Planchenault, and Christov, F. Poron, and Dr. Gherardi): GERMEN, EA2347 Université Paris 12, Val-de-Marne; the Service de Neurologie (Dr. Créange) and the Département de Pathologie (Dr. Gherardi), Centre Hospitalier Universitaire Henri Mondor, Créteil; and the Service de Réanimation Médicale (Drs. Sharshar and Raphaël), Hôpital Raymond Poincaré, Garches, France.

Address correspondence and reprint requests to Dr. Alain Créange, Service de Neurologie, Centre Hospitalier Universitaire Henri Mondor, 94010 Créteil Cedex, 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-Barré 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.

Key words: Metalloproteinase—Inflammation—Demyelinating neuropathy—Guillain-Barré syndrome.

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