title: Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-Neurofascin 155 antibodies.
abstract: Antibodies to Contactin-1 and Neurofascin 155 (Nfasc155) have recently been associated with subsets of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Contactin-1 and Nfasc155 are cell adhesion molecules that constitute the septate-like junctions observed by electron microscopy in the paranodes of myelinated axons. Antibodies to Contactin-1 have been shown to affect the localization of paranodal proteins both in patient nerve biopsies and in animal models after passive transfer. However, it is unclear whether these antibodies alter the paranodal ultrastructure. We examined by electron microscopy sural nerve biopsies from two patients presenting with anti-Nfasc155 antibodies, and also four patients lacking antibodies, three normal controls, and five patients with other neuropathies. We found that patients with anti-Nfasc155 antibodies presented a selective loss of the septate-like junctions at all paranodes examined. Further, cellular processes penetrated into the expanded spaces between the paranodal myelin loops and the axolemma in these patients. These patients presented with important nerve conduction slowing and demyelination. Also, the reactivity of anti-Nfasc155 antibodies from these patients was abolished in neurofascin-deficient mice, confirming that the antibodies specifically target paranodal proteins. Our data indicate that anti-Nfasc155 destabilizes the paranodal axo-glial junctions and may participate in conduction deterioration.
authors.affiliation: Department of Neurology and 'Centre de Référence des neuropathies rares', CHU Limoges, Limoges, France. Electronic address: jean-michel.vallat@unilim.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vallat
authors.affiliation: Department of Neurology, Mishima Hospital, Niigata, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
authors.affiliation: Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Kokubun
authors.affiliation: Department of Neurology, National Hospital Organization Minami-Kyoto Hospital, Joyo, Kyoto, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oka
authors.affiliation: Department of Neurology, Nerve-Muscle Unit, CHU Bordeaux (Groupe hospitalier Pellegrin), Place Amélie Raba-Léon, 33000 Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mathis
authors.affiliation: Department of Neurology and 'Centre de Référence des neuropathies rares', CHU Limoges, Limoges, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Magy
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Sherman
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M-UMR 7286, Marseille, France.
authors.forename: Jérôme J
authors.initials: JJ
authors.lastname: Devaux
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015815:Cell Adhesion Molecules / Q000276:immunology*; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000276:immunology*; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011901:Ranvier's Nodes / Q000473:pathology*; D013497:Sural Nerve / Q000473:pathology
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; C054305:NFASC protein, human; D009414:Nerve Growth Factors
keywords: Autoantibody; NF155; Node of Ranvier