Neurofascin as target of autoantibodies in Guillain–Barré syndrome

Extract

Sir, We have read with great interest the McGonigal et al. (2010) article, which addresses the pathogenic role of GD1a antibodies and complement activation for node of Ranvier dysfunction. Nodal injury might explain several electrophysiological features and clinical symptoms in patients with Guillain–Barré syndrome including the sometimes rapid recovery from paralysis. In our opinion, the reported mechanisms by which loss of axonal conduction can occur, may account not only for GD1a, but also for further nodal proteins once patients with Guillain–Barré syndrome develop antibodies against them. We therefore analysed sera from patients with Guillain–Barré syndrome for the presence of autoantibodies against two important nodal targets, neurofascin and contactin, and identified autoimmunity against the axonal and glial cell adhesion molecule neurofascin.

Sera were obtained from 52 patients with Guillain–Barré syndrome [43% female, mean (SD) age 53.4 (17.7) years] and 44 healthy volunteers [54% female, mean age 42.7 (19.1) years] with informed consent as published (Görtzen et al., 1999). Patients and controls did not significantly differ in serum albumin [3995 (951) versus 4238 (254) mg/dl, P = 0.42] or serum IgG concentrations [1111 (244) versus 982 (204) mg/dl, P = 0.08]. Antibody titres were determined using enzyme linked immunosorbent assay with recombinant rat neurofascin or human contactin-2 protein (R&D Systems) and specificity was confirmed by western blots (Fig. 1A). Serum neurofascin-IgG levels were significantly elevated compared with controls (P = 0.0019, Mann–Whitney test, two-tailed), while IgG levels against contactin-2 were not different (P = 0.27, Fig. 1B).