Immunotherapy for anti-GQ1b IgG antibody-mediated disorders: role of electrophysiology in human trials

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Sir, We read with interest the use of eculizumab as a protection against complement-mediated damage in a murine model of the Miller Fisher syndrome (MFS). This monoclonal antibody not only resulted in protection against functional and morphological terminal motor neuropathy, but effectively prohibited respiratory muscle paralysis (Halstead et al., 2008). These important findings have provided the basis for human trials in MFS, its related disorders of Bickerstaff's brainstem encephalitis (BBE) and Guillain-Barré syndrome (GBS), as well as neuropathies in which antibody-mediated complement activation may be pathophysiologically important (Compston, 2008; Lehmann and Hartung, 2008).

MFS, BBE and GBS are now widely regarded as part of a continuous spectrum of disorders whereby anti-GQ1b IgG antibody plays a vital part in the pathogenesis, although other antibody involvement may be contributory (Odaka et al., 2001; Lo, 2007). Evidence of anti-GQ1b IgG antibody binding to nodes of Ranvier (Chiba et al., 1993) and presynaptic terminals neuromuscular junctions, leading to complement-dependent cytoxicity, has been a great step forward in our understanding of these conditions (O’Hanlon et al., 2001).