In Vitro IVIG Anti-Complement Activity Points to Potential Mechanism of Action in MMN

While the pathogenesis of multifocal motor neuropathy (MMN) has yet to be established, anti-GM1 IgM antibodies are often identified in these patients, suggesting an autoimmune process involving complement. Intravenous immunoglobulin (IVIG) is a first-line treatment for MMN, but its mechanism of action is unknown.

Japanese investigators designed in vitro experiments to test 1) whether anti-GM1 IgM antibodies found in sera of MMN patients mediate complement activation that may trigger nerve cell damage, and 2) whether IVIG inhibits this complement activation.

Sera with reactive IgM antibodies against GM1 were obtained from 13 patients with MMN.Anti-GM1 IgM antibodies mediated deposition of four key complement proteins — C1q, C4b, C3b and C5b-9 — in GM1-coated microtiter plate wells. The deposition of complement was highly correlated with anti-GM1 IgM antibody titer. Introduction of IVIG into the wells dose-dependently reduced the deposition of these complement components.

These results, together with earlier data, suggest that IgMinduced, complement-mediated nodal injury of peripheral motor nerves generates conduction block and accounts for muscle weakness, according to the authors. The ability of IVIG to inhibit this type of complement activation in vitro suggests that in vivo it may act to reduce membrane attack complexmediated damage, leading to improved muscle strength.