Lipopolysaccharides from Campylobacter jejuni associated with Guillain-Barré syndrome patients mimic human gangliosides in structure

Abstract

Lipopolysaccharides extracted from Campylobacter jejuni serostrains (serotype reference strains) for serotypes 0:4 and 0:19 were found to have core oligosaccharides with terminal structures resembling human gangliosides GM, and GD1a. High-molecular-weight molecules that reflected the presence of 0 chains were shown in immunoblots to be immunologically specific for each serostrain. The 0:19 antiserum also reacted strongly with core oligosaccharides of two isolates from patients with Guillain-Barre syndrome (GBS), but the banding patterns and molecular structures were different from those of the 0:19 serostrain. A neuraminobiose disaccharide unit is attached to the terminal Gal residue in one isolate, and the other isolate lacked terminal N-acetyl glucosamine and galactose with attached sialic acid so that the sialic acid residues were present in a neuraminobiose unit linked to the only remaining galactose. Analysis of the high-Mr lipopolysaccharides of the 0:19 serostrain and the two isolates from GBS patients revealed the presence of a hyaluronic acid-like polymer with disaccharide-repeating units consisting of P-D-glucuronic acid amidated with 2-amino-2-deoxyglycerol and N-acetyl glucosamine. The results confirm a potential role for the core oligosaccharides in the etiology of GBS but also suggest that the 0-chain polysaccharide may be a contributing factor.

Campylobacter jejuni abscess, encephalomyelitis, and acute polyradiculoneuropathy

“…Molecular mimicry between C. jejuni lipo-oligosaccharide (LOS) and GM1 ganglioside has been established as one of the disease mechanisms of GBS. 2,15 In our patient, acute polyradiculoneuropathy was confirmed by clinical examination and electrophysiological studies, and high titers of anti-GM1 (IgG and IgM) antibodies further supported the diagnosis. Other antibodies, such as anti-GD1a, anti-GD1b, and anti-GQ1b, were not examined.…”

The role of infections in autoimmune disease

“…In addition, there is mounting evidence suggesting that lipopolysaccharide (LPS) on the outer core of the bacteria can mimic host gangliosides. LPS from C. jejuni serotypes associated with GBS were shown to resemble human gangliosides structurally [187,188], and priming of mice, rats and rabbits with the above-mentioned LPS produced corresponding anti-ganglioside antibodies [189][190][191]. Several studies have shown that C. jejuni serotypes associated with GBS are more likely to contain ganglioside-like epitopes compared with serotypes isolated from C. jejuni-infected patients with gastroenteritis but no neurological symptoms, with one study linking ganglioside mimicry to specific GBS clinical subtypes [192,193].…”

Stimulation of peripheral blood lymphocytes with Campylobacter jejuni generates a γδ T cell response in patients with Guillain–Barré syndrome

“…Several studies have suggested that immune recognition of cross-reacting epitopes on antigens common to C. jejuni and peripheral nerve myelin might provide a possible mechanism by which an autoreactive response leads to demyelination [1,4]. Support for a such an autoimmune etiology comes from recent reports of structural similarity between the lipopolysaccharide (LPS) of C. jejuni strains isolated from GBS patients and the peripheral nerve gangliosides GM1, GQ1b and GD1a [5,6]. Antibodies to these gangliosides, present in about 30% of GBS patients, have also been found to show cross-reactivity to C. jejuni LPS [5,6].…”

“…Support for a such an autoimmune etiology comes from recent reports of structural similarity between the lipopolysaccharide (LPS) of C. jejuni strains isolated from GBS patients and the peripheral nerve gangliosides GM1, GQ1b and GD1a [5,6]. Antibodies to these gangliosides, present in about 30% of GBS patients, have also been found to show cross-reactivity to C. jejuni LPS [5,6].…”