Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy
Por:
Delmont, E, Manso, C, Querol, L, Cortese, A, Berardinelli, A, Lozza, A, Belghazi, M, Malissart, P, Labauge, P, Taieb, G, Yuki, N, Illa, I, Attarian, S, Devaux, JJ
Publicada:
1 jul 2017
Resumen:
Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.
Filiaciones:
Delmont, E:
Aix Marseille Univ, Timone Univ Hosp, Referral Ctr ALS & Neuromuscular Dis, Marseille, France
Aix Marseille Univ, CNRS, CRN2M UMR7286, Marseille, France
Manso, C:
Aix Marseille Univ, CNRS, CRN2M UMR7286, Marseille, France
Querol, L:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Cortese, A:
IRCCS, C Mondino Natl Neurol Inst, Pavia, Italy
Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Ctr Neuromuscular Dis, MRC, Queen Sq, London, England
Berardinelli, A:
IRCCS, C Mondino Natl Neurol Inst, Pavia, Italy
Lozza, A:
IRCCS, C Mondino Natl Neurol Inst, Pavia, Italy
Labauge, P:
Montpellier Univ Hosp Ctr, Dept Neurol, Gui de Chauliac Hosp, Montpellier, France
Taieb, G:
Montpellier Univ Hosp Ctr, Dept Neurol, Gui de Chauliac Hosp, Montpellier, France
Yuki, N:
Mishima Hosp, Dept Neurol, Niigata, Japan
Illa, I:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Attarian, S:
Aix Marseille Univ, Timone Univ Hosp, Referral Ctr ALS & Neuromuscular Dis, Marseille, France
Devaux, JJ:
Aix Marseille Univ, CNRS, CRN2M UMR7286, Marseille, France
Bronze
|