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The immunopathogenesis of Miller Fisher syndrome
1University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland, UK. gora13@udcf.gla.ac.uk
Abstract:
Over the past decade, remarkable progress has been made in our understanding of the pathogenesis of Miller Fisher syndrome (MFS), a clinical variant of Guillain Barré syndrome (GBS). MFS comprises the clinical triad of ataxia, areflexia and ophthalmoplegia. It is associated with acute-phase IgG antibodies to GQ1b and GT1a gangliosides in over 90% of cases which are highly disease specific. Like GBS, MFS is a post-infectious syndrome following diverse infections, but particular attention has been paid to its association with Campylobacter jejuni enteritis. Serostrains of C. jejuni isolated from infected patients bear ganglioside-like epitopes in their lipopolysaccharide core oligosaccharides, which elicit humoral immune responses exhibiting molecular mimicry with GQ1b/GT1a gangliosides. These antibodies are believed to be the principal cause of the syndrome and physiological studies aimed at proving this have focused on the motor-nerve terminal as a potential site of pathogenic action. This review describes these findings and formulates a pathogenesis model based on our current state of knowledge.
Insights
Miller Fisher syndrome (MFS), a Guillain Barré syndrome variant, involves ataxia, ophthalmoplegia, and areflexia. Pathogenesis involves antibodies to gangliosides GQ1b/GT1a, often triggered by Campylobacter jejuni infections.
Area of Science:
- Neurology
- Immunology
- Microbiology
Background:
- Miller Fisher syndrome (MFS) is a rare variant of Guillain Barré syndrome (GBS).
- MFS is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia.
- Over 90% of MFS cases show acute-phase IgG antibodies targeting GQ1b and GT1a gangliosides.
Purpose of the Study:
- To review recent advancements in understanding MFS pathogenesis.
- To elucidate the role of specific antibodies and infectious triggers in MFS.
- To propose a model for MFS pathogenesis.
Main Methods:
- Literature review of studies on MFS pathogenesis.
- Analysis of the association between MFS, ganglioside antibodies (GQ1b/GT1a), and Campylobacter jejuni infections.
- Examination of physiological studies investigating antibody targets.
Main Results:
- MFS pathogenesis is linked to IgG antibodies against GQ1b and GT1a gangliosides.
- Campylobacter jejuni enteritis is a significant preceding infection.
- Molecular mimicry between C. jejuni lipopolysaccharide epitopes and gangliosides triggers antibody production.
Conclusions:
- Antibodies to GQ1b/GT1a gangliosides, induced by infections like C. jejuni via molecular mimicry, are the primary cause of MFS.
- The motor-nerve terminal is a key site for pathogenic antibody action.
- Current knowledge supports a model of post-infectious autoimmunity in MFS pathogenesis.