Association of Anti-GT1a Antibodies with an Outbreak of Guillain-Barré Syndrome and Analysis of Ganglioside Mimicry in an Associated Campylobacter jejuni Strain.

Maojun Zhang,Jianjun Li,Nobuhiro Yuki,Fanliang Meng,Michel Gilbert,Hongying Liu,Fangfang Cao,Qun Li,Jianzhong Zhang

doi:10.1371/journal.pone.0131730

Abstract

An outbreak of Guillain-Barré syndrome (GBS), subsequent to Campylobacter jejuni enteritis, occurred in China in 2007. Serum anti-ganglioside antibodies were measured in GBS patients and controls. Genome sequencing was used to determine the phylogenetic relationship among three C. jejuni strains from a patient with GBS (ICDCCJ07001), a patient with gastroenteritis (ICDCCJ07002) and a healthy carrier (ICDCCJ07004), which were all associated with the outbreak. The ganglioside-like structures of the lipo-oligosaccharides of these strains were determined by mass spectrometry. Seventeen (53%) of the GBS patients had anti-GT1a IgG antibodies. GT1a mimicry was found in the lipo-oligosaccharides of strain ICDCCJ07002 and ICDCCJ07004; but a combination of GM3/GD3 mimics was observed in ICDCCJ07001, although this patient had anti-GT1a IgG antibodies. A single-base deletion in a glycosyltransferase gene caused the absence of GT1a mimicry in ICDCCJ07001. The phylogenetic tree showed that ICDCCJ07002 and ICDCCJ07004 were genetically closer to each other than to ICDCCJ07001. C. jejuni, bearing a GT1a-like lipo-oligosaccharide, might have caused the GBS outbreak and the loss of GT1a mimicry may have helped ICDCCJ07001 to survive in the host.

Highlights

Guillain-Barré syndrome (GBS) is currently the most frequent cause of acute flaccid paralysis worldwide, since the near elimination of poliomyelitis [1]
The IgGs in the sera from the GBS patients had stronger reactions with the LOS from C. jejuni ICDCCJ07002 than with the LOS from strain ICDCCJ07001 (Fig 1, the x-axis indicates the ID of the serum samples and the y-axis indicates the value of the optical density (OD) at 450 nm; red bar for anti07002 LOS reaction and blue bar for anti-07001 LOS reaction)
We found that half of the 32 patients with GBS had anti-GT1a IgG antibodies without GQ1b reactivity

Summary

Introduction

Guillain-Barré syndrome (GBS) is currently the most frequent cause of acute flaccid paralysis worldwide, since the near elimination of poliomyelitis [1]. The anti-ganglioside antibodies bind to gangliosides such as GM1 and GD1a, which are strongly expressed at the nodes of Ranvier, and activate the complement system, leading to the formation of membrane-attached complexes at the nodal axolemma of peripheral motor fibres. This results in the disappearance of voltage-gated sodium channels at the nodes and the disruption of axo-glial junctions, followed by a failure of motor nerve conduction and muscle weakness [6,7]. Strains having the same class of LOS locus can express different ganglioside mimics because of DNA sequence polymorphisms in the cst-II, cgtA and cgtB genes, in addition to other genes encoding glycosyltransferases, involved in the biosynthesis of the LOS outer core [12,13,14]. Strains with cst-II (Asn51) produce ganglioside mimics containing both α-2,3- and α-2,8-linked NeuAc residues such as GT1a-, GD3-like and GD1c-like LOS [13,15,16]

Methods

Results

Conclusion