Anti-Ganglioside Antibodies Induce Nodal and Axonal Injury via Fcγ Receptor-Mediated Inflammation

Abstract

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune neuropathy and anti-ganglioside antibodies (Abs) are strongly associated with this disorder. Several studies have implied that specific anti-ganglioside Abs induce neuropathy in patients with axonal forms of GBS. To study the mechanisms of anti-ganglioside Abs-induced neuropathy, we established a new passive transfer mouse model by L5 spinal nerve transection (L5SNT; modified Chung's model) and systemic administration of anti-ganglioside Abs. L5SNT causes degeneration of a small proportion of fibers that constitute sciatic nerve and its branches, but importantly breaks the blood-nerve barrier, which allows access to circulating Abs and inflammatory cells. Our studies indicate that, in this mouse model, anti-ganglioside Abs induce sequential nodal and axonal injury of intact myelinated nerve fibers, recapitulating pathologic features of human disease. Notably, our results showed that immune complex formation and the activating Fc gamma receptors (FcγRs) were involved in the anti-ganglioside Abs-mediated nodal and axonal injury in this model. These studies provide new evidence that the activating FcγRs-mediated inflammation plays a critical role in anti-ganglioside Abs-induced neuropathy (injury to intact nerve fibers) in GBS.

Keywords: Fc gamma receptors; Guillain-Barré syndrome; anti-ganglioside antibody; blood–nerve barrier; macrophage; nodal and axonal injury.