A Multifocal Approach: Toward the Production of Complement-activating MMN Patient-derived Anti-GM1 Antibodies

Abstract

Multifocal Motor Neuropathy (MMN) is a rare, chronic, primarily inflammatory complement-mediated polyneuropathy. It is characterized by progressive distal limb weakness. The exact pathophysiology of MMN remains unknown, however an important feature is that it can occur due to complement activation via IgM antibodies that bind to the ganglioside GM1. Other anti-GM1 antibody classes, such as IgG, have also been reported in MMN patients. The current approved therapy is with intravenous immunoglobulin (IVIg), however recent focus has shifted to complement inhibition as a novel treatment strategy. As MMN has a varied phenotype, which may be differentially triggered by different classes of antibodies, this study aimed to produce and purify MMN patient-derived human IgM and IgG anti-GM1 antibodies, in order to test how they impact the complement system. We showed that it is possible to produce IgG anti-GM1 which can bind to motor neurons. Ultimately, however, we were unable to produce structurally and functionally reliable IgM anti-GM1.