Neurology 2014 Mar 12;82(10):879-86. Epub 2014 Feb 12.
From the Neuromuscular Diseases Unit (L.Q., G.N.-G., R.R.-G., J.D.-M., E.G., R.B., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Centro para la Investigación Biomédica en Red en Enfermedades Neurodegenerativas (L.Q., G.N.-G., R.R.-G., J.D.-M., M.J.S., E.G., J.B., I.I.), CIBERNED, Madrid; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela; Department of Neurology (A.O.-M.), Hospital Virgen de las Nieves, Granada; Department of Neurology (M.J.S., J.B.), University Hospital Marqués de Valdecilla (IFIMAV) and University of Cantabria; Department of Neurology (J.D.), Hospital Clinic, Universitat de Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona; and Institució Catalana de Recerca i Estudis Avançats (J.D.), Barcelona, Spain.
Objective: To describe the frequency of antibodies against neurofascin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the associated clinical features.
Methods: Immunocytochemistry was used to identify antibodies to neurofascin 155 (NF155) and 186. Serum reactivity with paranodes and brain tissue was tested with immunohistochemistry of teased-nerve fibers and rat brain. Antibody titers and immunoglobulin (Ig) G isotypes were determined using ELISA. Clinical information was obtained retrospectively.
Results: Two of 53 patients, but none of 204 controls, had antibodies to NF155 (p = 0.041). The 2 patients with NF155 antibodies developed severe polyradiculoneuropathy with predominant distal weakness that was refractory to IVIg. Eight additional patients with IVIg-refractory CIDP were then identified from a national database; 2 of them with the same clinical features also had NF155 antibodies. Overall, 3 of the 4 patients with NF155 antibodies had a disabling and characteristic tremor (high amplitude, low frequency, postural, and intention). Patients' antibodies reacted with the paranodes in teased-nerve fibers and with the neuropil of rat cerebellum, brain, and brainstem. Anti-NF155 antibodies were predominantly of the IgG4 isotype in all patients.
Conclusion: Patients with CIDP positive for IgG4 NF155 antibodies constitute a specific subgroup with a severe phenotype, poor response to IVIg, and disabling tremor. Autoantibodies against paranodal structures associate with distinct clinical features in CIDP and their identification has diagnostic, prognostic, and therapeutic implications.
Classification Of Evidence: This study provides Class IV evidence that autoantibodies to NF155 identify a CIDP subtype characterized by severe neuropathy, poor response to IVIg, and disabling tremor.