What are the causes of Guillain-Barré Syndrome (GBS)?

From the Guidelines

Guillain-Barré syndrome (GBS) is primarily caused by an abnormal immune response that attacks the peripheral nerves, triggered by preceding infections, such as Campylobacter jejuni, cytomegalovirus, and Zika virus, as well as other factors like vaccinations and surgical procedures, as reported in the most recent study 1. The most common trigger is a preceding infection, typically occurring 1-3 weeks before GBS symptoms develop. Some key points to consider are:

• Gastrointestinal infections with Campylobacter jejuni bacteria are the most frequently identified cause, accounting for about 30% of cases.
• Other infectious triggers include cytomegalovirus, Epstein-Barr virus, influenza virus, and COVID-19.
• In rare cases, GBS can develop following vaccinations, though this risk is extremely small compared to the risk of developing GBS after natural infections, with an estimated increase of approximately one additional GBS case per one million vaccinations 1.
• Surgical procedures and certain medications have also been associated with GBS in some cases.
• The underlying mechanism involves molecular mimicry, where the immune system produces antibodies against infectious agents that cross-react with components of peripheral nerve tissue, particularly the myelin sheath or axons, as described in 1.
• This immune attack leads to inflammation and damage to the peripheral nerves, causing the characteristic muscle weakness and sensory abnormalities of GBS.
• About 30% of cases have no identifiable preceding event, suggesting that other unknown factors may also trigger this autoimmune response. It is essential to note that the pathogenesis of GBS is not fully understood, and the exact mechanisms by which these triggers lead to the development of GBS are still being researched, as mentioned in 1.

From the Research

Causes of Guillain-Barré Syndrome

The causes of Guillain-Barré Syndrome (GBS) are complex and multifaceted. Some of the key factors that contribute to the development of GBS include:

• Previous infections, which are thought to trigger GBS in approximately three-quarters of cases 2, 3
• Specific infectious agents, such as:
  • Campylobacter jejuni (C. jejuni), which is responsible for about a third of GBS cases 2, 4
  • Mycoplasma pneumoniae 2, 3
  • Cytomegalovirus 2, 3
  • Haemophilus influenzae 3
• Molecular mimicry, where the immune system mistakes components of the myelin sheath or axolemma for pathogens, leading to an autoimmune response 2, 3
• Genetic factors, which may play a role in determining an individual's susceptibility to GBS 5
• Environmental factors, such as vaccination, although the risk of GBS associated with vaccination is considered to be very low 3

Infectious Triggers

Infections are thought to play a key role in the development of GBS. Some of the most common infectious triggers include:

• Campylobacter infection, which is strongly associated with GBS 4
• Cytomegalovirus infection 2, 3
• Mycoplasma pneumoniae infection 2, 3
• Haemophilus influenzae infection 3

Pathophysiology

The pathophysiology of GBS is complex and involves an immune-mediated response to components of the myelin sheath or axolemma. Some of the key mechanisms involved include:

• Autoantibody production, where the immune system produces antibodies against components of the myelin sheath or axolemma 2, 5
• Activation of macrophages and T cells, which contribute to the immune response 5
• Molecular mimicry, where the immune system mistakes components of the myelin sheath or axolemma for pathogens, leading to an autoimmune response 2, 3