Lorena Martín-Aguilar1, Elba Pascual-Goñi1, Cinta Lleixà1, Marina Frasquet1, Herminia Argente1, Angel Cano-Abascal1, Jordi Diaz-Manera1, Elena Cortés-Vicente1, Ana Lara Pelayo-Negro1, Teresa Sevilla1, Ricard Rojas-García1, Luis Querol2. 1. From the Neuromuscular Diseases Unit, Department of Neurology (L.M.-A., E.P.-G., C.L., J.D.-M., E.C.-V., R.R.-G., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Department of Neurology (M.F., H.A., T.S.), Hospital Universitari i Politècnic La Fe, Valencia; Service of Neurology (A.C.-A., A.L.P.-N.), University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander; Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (J.D.-M., R.-R.G., L.Q.), Madrid; and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) (A.L.P.-N.), Santander, Spain. 2. From the Neuromuscular Diseases Unit, Department of Neurology (L.M.-A., E.P.-G., C.L., J.D.-M., E.C.-V., R.R.-G., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Department of Neurology (M.F., H.A., T.S.), Hospital Universitari i Politècnic La Fe, Valencia; Service of Neurology (A.C.-A., A.L.P.-N.), University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander; Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (J.D.-M., R.-R.G., L.Q.), Madrid; and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) (A.L.P.-N.), Santander, Spain. lquerol@santpau.cat.
Abstract
OBJECTIVE: To study the presence of nodal and paranodal immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in patients with genetic neuropathies. METHODS: A total of 108 patients with genetic neuropathies from 3 different centers were included. The presence of IgG and IgM antibodies against neurofascin-155 (NF155), nodal neurofascin (NF186 and NF140), and contactin-1 (CNTN1) were investigated with a cell-based assay (CBA) using immunocytochemistry in transfected HEK293 cells. Sera with positive or uncertain results were further tested by ELISA and immunohistochemistry in pig teased-nerve fibers. RESULTS: Six patients with Charcot-Marie-Tooth disease (CMT) had an uncertain staining pattern for IgM against nodal neurofascin that was not confirmed by ELISA. Two patients with CMT had an uncertain staining pattern for IgG against nodal neurofascin that was not confirmed by ELISA or immunohistochemistry. One patient with CMT with a confirmed GJB1 mutation tested positive for IgG against NF155 by CBA and ELISA (1/900), but was not confirmed by immunohistochemistry and was ultimately classified as negative. CONCLUSIONS: Antibodies against nodal or paranodal antigens were not detected in our cohort of patients with CMT, as previously reported. Some patients may falsely test positive for any of the techniques; confirmatory techniques should be incorporated into the routine testing.
OBJECTIVE: To study the presence of nodal and paranodal immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in patients with genetic neuropathies. METHODS: A total of 108 patients with genetic neuropathies from 3 different centers were included. The presence of IgG and IgM antibodies against neurofascin-155 (NF155), nodal neurofascin (NF186 and NF140), and contactin-1 (CNTN1) were investigated with a cell-based assay (CBA) using immunocytochemistry in transfected HEK293 cells. Sera with positive or uncertain results were further tested by ELISA and immunohistochemistry in pig teased-nerve fibers. RESULTS: Six patients with Charcot-Marie-Tooth disease (CMT) had an uncertain staining pattern for IgM against nodal neurofascin that was not confirmed by ELISA. Two patients with CMT had an uncertain staining pattern for IgG against nodal neurofascin that was not confirmed by ELISA or immunohistochemistry. One patient with CMT with a confirmed GJB1 mutation tested positive for IgG against NF155 by CBA and ELISA (1/900), but was not confirmed by immunohistochemistry and was ultimately classified as negative. CONCLUSIONS: Antibodies against nodal or paranodal antigens were not detected in our cohort of patients with CMT, as previously reported. Some patients may falsely test positive for any of the techniques; confirmatory techniques should be incorporated into the routine testing.
Authors: Desiree De Simoni; Gerda Ricken; Michael Winklehner; Inga Koneczny; Michael Karenfort; Ulf Hustedt; Ulrich Seidel; Omar Abdel-Mannan; Pinki Munot; Simon Rinaldi; Claudia Steen; Michael Freilinger; Markus Breu; Rainer Seidl; Markus Reindl; Julia Wanschitz; Cinta Lleixà; Günther Bernert; Klaus-Peter Wandinger; Ralf Junker; Luis Querol; Frank Leypoldt; Kevin Rostásy; Romana Höftberger Journal: Neurol Neuroimmunol Neuroinflamm Date: 2020-06-02