Multifocal motor neuropathy: association of anti-GM1 IgM antibodies with clinical features

To determine the prevalence and specificity of antibodies against single gangliosides and ganglioside complexes in serum from 88 patients with multifocal motor neuropathy (MMN) and to study the association with clinical features.

ELISA was used to detect immunoglobulin (Ig)M, IgG, and IgA antibodies against GM1, GM2, GD1a, GD1b, GM1b, GT1a, GT1b, GQ1b, GalNAc-GD1a, and the glycolipid SGPG; absorption studies were performed to study cross-reactivity. Presence of antibodies against ganglioside complexes consisting of any of combinations of GM1, GM2, GD1a, GD1b, GT1b, and GQ1b was also tested.

Anti-GM1 IgM, IgG, and IgA antibodies were detected in serum from 43%, 1%, and 5% of patients with MMN. Anti-GM2 IgM antibodies were detected in 6% and anti-GD1b IgM antibodies in 9% of patients. Patients with MMN with anti-GM1 IgM antibodies had more severe weakness (p < 0.01), more disability (p < 0.01), and more axon loss (p = 0.05) than patients without anti-GM1 IgM antibodies. Anti-GM1 IgM antibody titers correlated with Medical Research Council scores (correlation coefficient = 0.43; p < 0.0001). Anti-GD1b IgM antibody activity was associated with reduced vibration sense (p < 0.01). Absorption studies showed that anti-GD1b and anti-GM2 IgM antibodies cross-reacted with GM1. Antibodies against ganglioside complexes were not detected. Complexes containing GD1a, GD1b, GT1b, or GQ1b with GM1 lowered antibody activity against GM1.

Anti-ganglioside IgM antibodies in MMN display limited specificity and are associated with severity and clinical characteristics. Results of this study suggest that anti-GM1 IgM antibodies may play a role in MMN pathogenesis.