The Guillain-Barré syndrome (s)(GBS [s]) comprises various forms of acute flaccid paralysis caused by an autoimmune attack against components of the peripheral nerve. 1, 2 The most common pattern is the acute inflammatory demyelinating polyneuropathy (AIDP), in which the putative target antigens are on the myelin sheath. The least common, but better understood forms, are the acute motor (or motor-sensory) axonal neuropathy (AMAN or AMSAN) and the Miller-Fisher syndrome (MFS) with target antigens on motor nerve terminals and axons. Humoral and cell-mediated mechanisms participate in the cause of GBS (s) probably triggered by molecular mimicry between bacterial or viral glycoconjugates and nerve gangliosides. 3, 4 In AIDP, autoreactive T cells may initiate the lesion, but the effector mechanisms are complement deposits and macrophages invading the myelin sheath. In AMAN and MFS, immunoglobulin G (IgG) antibodies against specific gangliosides (GM1, GM1a, GalNac-GD1a, and GM1b in AMAN; GQ1b in MFS) block functionally relevant epitopes for nerve conduction5–8 or neuromuscular transmission9, 10 resulting in axonal injury by an antibody-dependent cellular cytotoxic process. Furthermore, rabbits immunized with GM1 develop AMAN. 11

Therapeutically, the self-limiting course of GBS (s) is significantly shortened by intravenous immunoglobulin (IVIg) or plasmapheresis. The results from these therapies are gratifying, but the mode by which they exert their immunomodulatory action remains a fascinating immunological puzzle. Although plasmapheresis removes circulating immune factors responsible for conduction block, IVIg manipulates the immune system to modify or neutralize these factors either in situ or in the circulation. 12, 13 In this issue, Buchwald and colleagues insightfully demonstrate that in patients with GBS, IVIg exerts a neutralizing effect on the activity of blocking antibodies. 14 They showed, by means of a perfused macropatch clamp electrode in a mouse nerve-muscle preparation, that serum from AMAN and MFS patients contains IgG antibodies that “block” quantal release, confirming their own work. 9 These