The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome

Abstract

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissueis considered to induce cross-reactive antibodies that lead to Guillain-Barré syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.

The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and Immunological Profiling of Physiological Fluids

“…Immunological profiling of 88 GBS patients-Although the crucial role of Campylobacter jejuni is well established for AMAN (48), for AIDP there is a questionable link with pathogenesis and different viral infections like CMV (49) or EBV (50). Importantly, peptidomic/proteomic profiling of CSF obtained from AIDP patients revealed evident signs of the proteins involved in antiviral defense.…”

Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

“…The pathogens then could use a mutation strategy to evade the immune response. The identification of genes involved in LOS synthesis and the study of their regulation are emerging areas of research for a better understanding of the pathogenic mechanisms used by these bacteria (23,25). Several researchers have reported that ganglioside-like LOSs are synthesized by sialyltransferase Cst-II, ␤-1,4-N-acetylgalactosaminyl-transferase CgtA, and ␤-1,3-galactosyltransferase CgtB and that there is strong association between these genes and GBS-associated C. jejuni strains.…”

“…Godschalk et al (25) demonstrated for the first time that specific bacterial genes are crucial for induction of antiganglioside antibodies, determining the class of LOS loci (classes A to E) in a collection of 21 neuropathy-associated and 21 control C. jejuni strains isolated from patients with uncomplicated enteritis. Analyzing the expression of ganglioside-like structures in relation to the class of LOS locus, Godschalk et al (25) found that GM1-like structures were associated with a class A locus, whereas GQ1b-like structures were predominantly expressed in strains with a class B locus.…”

“…Analyzing the expression of ganglioside-like structures in relation to the class of LOS locus, Godschalk et al (25) found that GM1-like structures were associated with a class A locus, whereas GQ1b-like structures were predominantly expressed in strains with a class B locus. In 8 of 11 strains with a class D or E locus, ganglioside-like structures were not detected, which is in accord with the absence of genes involved in the biosynthesis or transfer of sialic acid.…”

Sialylation of Campylobacter jejuni Endotoxin Promotes Dendritic Cell–Mediated B Cell Responses through CD14-Dependent Production of IFN-β and TNF-α

“…The GB11 Campylobacter sialyltransferase-II (cst-II) mutant strain lacking sialic acids was described previously (21). GB19 was isolated from a patient with Miller Fisher syndrome and has a GD1c-mimicking LOS (20).…”