title: Antibodies to gliomedin cause peripheral demyelinating neuropathy and the dismantling of the nodes of Ranvier.
abstract: Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are conditions that affect peripheral nerves. The mechanisms that underlie demyelination in these neuropathies are unknown. Recently, we demonstrated that the node of Ranvier is the primary site of the immune attack in patients with GBS and CIDP. In particular, GBS patients have antibodies against gliomedin and neurofascin, two adhesion molecules that play a crucial role in the formation of nodes of Ranvier. We demonstrate that immunity toward gliomedin, but not neurofascin, induced a progressive neuropathy in Lewis rats characterized by conduction defects and demyelination in spinal nerves. The clinical symptoms closely followed the titers of anti-gliomedin IgG and were associated with an important deposition of IgG at nodes. Furthermore, passive transfer of antigliomedin IgG induced a severe demyelinating condition and conduction loss. In both active and passive models, the immune attack at nodes occasioned the loss of the nodal clusters for gliomedin, neurofascin-186, and voltage-gated sodium channels. These results indicate that primary immune reaction against gliomedin, a peripheral nervous system adhesion molecule, can be responsible for the initiation or progression of the demyelinating form of GBS. Furthermore, these autoantibodies affect saltatory propagation by dismantling nodal organization and sodium channel clusters. Antibodies reactive against nodal adhesion molecules thus likely participate in the pathologic process of GBS and CIDP.
authors.affiliation: National Center for Scientific Research (CNRS), Aix-Marseille University, Marseille, France. jerome.devaux@univ-amu.fr
authors.forename: Jérôme J
authors.initials: JJ
authors.lastname: Devaux
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology; D006801:Humans; D007109:Immunity / Q000276:immunology; D007114:Immunization; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000276:immunology* / Q000473:pathology*; D011901:Ranvier's Nodes / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D013126:Spinal Nerve Roots / Q000473:pathology
chemical_list: D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; D007074:Immunoglobulin G; C504359:gliomedin, rat