An anti‐ganglioside antibody‐secreting hybridoma induces neuropathy in mice

Immune responses against gangliosides are strongly implicated in the pathogenesis of some variants of Guillain–Barré syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related gangliosides are frequently present in patients with post‐ Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti‐ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti‐ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti‐ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti‐ganglioside antibody‐secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti‐ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood–nerve barrier studies indicate that animals implanted with hybridoma had leaky blood–nerve barrier compared to mice that received systemically administered anti‐ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody‐mediated injury play a role in the development of neuropathy. Ann Neurol 2004;56:228–239