Carbohydrate mimicry between human ganglioside GM1 and <i>Campylobacter jejuni</i> lipooligosaccharide causes Guillain–Barré syndrome

TLDR

Molecular mimicry between microbial and self-components is proposed to underlie postinfectious autoimmune diseases, yet direct evidence is scarce; Guillain–Barré syndrome, the most common acute neuromuscular paralysis, typically follows Campylobacter jejuni enteritis. The study demonstrates that the Campylobacter jejuni lipooligosaccharide mimics the human GM1 ganglioside carbohydrate, and immunization of mice produces a monoclonal antibody that reacts with GM1 and binds human peripheral nerves. Rabbits sensitized to the lipooligosaccharide produced anti‑GM1 IgG and exhibited flaccid limb weakness with neuropathology matching Guillain–Barré syndrome, while monoclonal and patient anti‑GM1 antibodies blocked muscle action potentials without causing paralysis, confirming carbohydrate mimicry as a key driver of autoimmune neuropathy.

Abstract

Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in postinfectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to carbohydrate structures. Guillain–Barré syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1–2 wk after various infections, in particular, Campylobacter jejuni enteritis. Carbohydrate mimicry [Galβ1–3GalNAcβ1–4(NeuAcα2–3)Galβ1-] between the bacterial lipooligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain–Barré syndrome, and conclusive evidence is reported here. On sensitization with C. jejuni lipooligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical with those present in Guillain–Barré syndrome. Immunization of mice with the lipooligosaccharide generated a mAb that reacted with GM1 and bound to human peripheral nerves. The mAb and anti-GM1 IgG from patients with Guillain–Barré syndrome did not induce paralysis but blocked muscle action potentials in a muscle–spinal cord coculture, indicating that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.