Guillain–Barre syndrome: First description of a snake envenomation aetiology

Abstract

Background

Guillain–Barre syndrome (GBS) is considered as an acute, immune-mediated polyradiculoneuropathy with different clinical phenotypes arising after viral or bacterial infections, vaccination or surgery. However, in 40% of GBS patients the aetiology remains unknown. In this manuscript, we report the occurrence of GBS in a patient bitten by a snake (Vipera aspis) for which a cross-reaction was shown between GM2 ganglioside and glycosidic epitopes of venom proteins.

Methods

The venom of the snake implied in the patient's envenomation was collected. Its composition was characterised by ELISA and SELDI-TOF MS. Cross-reactivities between venom proteins and GM2 gangliosides were identified by Western blot after immunoabsorption of patient's serum with increasing amounts of purified GM2. Enzymatic deglycosylation of the venom was performed to determine the specificity of the patient's serum cross-reaction.

Findings

We proved the absence of neurotoxicity of the viper venom. The patient's serum presented specific cross-reactions with several glycosylated venom proteins. After deglycolysation of these proteins, the patient's serum cross-reactivity was abolished. Furthermore, we compared the immune response to venom proteins of sera from two groups of patients. The first group showed IgM reactivity against GM2 ganglioside associated with GBS, and cross-reacted with venom proteins. The second group presented an IgM reactivity against CMV, without neurological disorders, and reacted with neither venom proteins nor gangliosides.

Interpretation

Our study proved the auto-immunological aetiology of GBS in our patient based on molecular mimicry mechanisms between venom proteins and GM2 ganglioside.

Introduction

Guillain–Barre syndrome (GBS) is considered as an acute, immune-mediated polyradiculoneuropathy having different clinical phenotypes arising after minor viral or bacterial infections, vaccination or surgery. Approximately 60% of patients with GBS have autoantibodies to specific epitopes present on gangliosides in the myelin sheath (Kusunoki et al., 1996, Willison and Yuki, 2002) and/or ganglioside complexes (Kaida et al., 2004). Immune responses directed towards gangliosides and their microbial mimics (bacterial or viral) are the only known mediators of this post-infection acute inflammatory polyradiculoneuropathy (Yuki, 2001). This was first demonstrated for GM1 ganglioside and Campylobacter jejuni (CJ) lipooligosaccharide (Yuki et al., 1993, Griffin et al., 1996), GM2 ganglioside and cytomegalovirus (CMV) glycans (Ang et al., 2002), and other components of myelin sheath, such as galactocerebroside, and Mycoplasma pneumoniae (Kusunoki et al., 1995). Yet, for 40% of GBS patients, the aetiology remains unknown. We report a case of GBS with a venomous aetiology: a 37-year-old man developed an acute flaccid tetraparesis, diagnosed as GBS, 17 days after envenomation by Vipera aspis aspis bite. Initial immunological investigations of our patient's serum showed an IgM reactivity against GM2 ganglioside, but IgM serology and polymerase chain reaction (PCR) against CMV, diagnosing a recent infection, were negative. We consequently investigated the hypothesis of an immunological cross-reaction between the venom proteins and GM2 ganglioside.