From the Guidelines
Guillain-Barré Syndrome (GBS) is primarily an autoimmune disorder where the immune system mistakenly attacks peripheral nerves through molecular mimicry, triggered by an antecedent infection, leading to demyelination or axonal damage and resulting in the characteristic clinical presentation of ascending paralysis, sensory abnormalities, and autonomic dysfunction. The exact immune pathophysiology of GBS involves an aberrant immune response to infections, which results in damage to peripheral nerves, as noted in a study published in Nature Reviews Neurology 1. This response is thought to be caused by the production of serum antibodies against gangliosides, which reside on the surface of peripheral nerves. The study highlights that GBS is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots, usually triggered by infections, such as Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, or Zika virus.
Some key points about the immune pathophysiology of GBS include:
- The immune system mistakenly attacks peripheral nerves through molecular mimicry, where antibodies produced against the pathogen cross-react with gangliosides and other components of peripheral nerves due to molecular similarity.
- The specific target of the autoimmune response determines the GBS variant, with myelin being primarily attacked in acute inflammatory demyelinating polyneuropathy (AIDP), the axonal membrane being targeted in acute motor axonal neuropathy (AMAN), and cranial nerves being predominantly affected in Miller Fisher syndrome.
- T-cells contribute to the immune response by releasing inflammatory cytokines that enhance the immune attack, leading to complement activation, macrophage recruitment, and subsequent demyelination or axonal damage, as discussed in the study 1.
- The resulting nerve damage disrupts signal transmission, causing the characteristic ascending paralysis, sensory abnormalities, and autonomic dysfunction seen in GBS patients, with disease progression being rapid and most patients reaching their maximum disability within 2 weeks, as noted in the study 1.
From the Research
Immune Pathophysiology of Guillain-Barré Syndrome (GBS)
The immune pathophysiology of GBS is complex and not fully elucidated. However, research suggests that it is an immune-mediated disorder characterized by acute paralysis and involvement of IgG autoantibodies and innate immune effectors 2. The exact mechanisms underlying GBS pathogenesis are still unclear, but it is thought to be triggered by a preceding bacterial or viral infection, which leads to an aberrant immune response that mistakenly attacks the nerve tissue of the host 3.
Molecular Mimicry and Autoantibodies
Molecular mimicry is a proposed mechanism for the induction of anti-ganglioside antibodies in GBS, where the immune system recognizes a molecularly similar epitope between microbial glycans and self-gangliosides 4. This leads to the production of autoantibodies, such as anti-GM1, anti-GD1a, and anti-GQ1b, which are associated with specific clinical phenotypes of GBS 4.
Immune-Mediated Pathogenesis
The immune-mediated pathogenesis of GBS involves the activation of complement and the formation of complement pores, which leads to axonal injury and nerve damage 4. The level of immunological tolerance to microbial glycans, ganglioside density in target tissue, and the role of calcium influx through complement pores are all determinants that influence disease expression 4.
Treatment and Therapeutic Targets
Immunomodulatory treatments, including intravenous immunoglobulins (IVIg) and plasma exchange (PE), are the first-line therapies for GBS, but their efficacy can be variable depending on the subtype and severity of the disease 5. New therapies, such as those targeting IgG autoantibody catabolism and complement activation, are being developed and may provide more potent options for GBS patients who do not respond to IVIg or PE 2.
Key Factors Influencing Disease Expression
- Level of immunological tolerance to microbial glycans that mimic self-gangliosides 4
- Ganglioside density in target tissue 4
- Level of complement activation and the neuroprotective effects of endogenous complement regulators 4
- Role of calcium influx through complement pores in mediating axonal injury 4
Current Understanding and Future Directions
The current understanding of GBS pathophysiology highlights the importance of immune-mediated mechanisms and the potential for targeted therapies 5. Further research is needed to fully elucidate the immune pathophysiology of GBS and to develop effective treatments for this debilitating disorder 2, 3, 5, 4.