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Table 2 Potential pathogenesis of GBS by infectious and non-infectious triggers

From: Is there a causal nexus between COVID-19 infection, COVID-19 vaccination, and Guillain-Barré syndrome?

Triggers of GBS

Potential pathogenesis

Infectious events

 Bacteria

  C. jejuni

Molecular mimicry (GM1 epitopes on LOS from C. jejuni) and cross-reactivity between C. jejuni and peripheral nerve gangliosides

  M. pneumoniae

Molecular mimicry between GM1 ganglioside and M. pneumoniae

  H. influenzae

Molecular mimicry: presence of GM1 and GQ1b epitopes in H. influenzae

  Salmonella species

Unclear

 Viruses

  CMV

Molecular mimicry: presence of GM2 and GD2 epitopes on CMV, homology between moesin (a cytoskeletal component, key role on myelination) and a CMV phosphoprotein

  HSV

Molecular mimicry: presence of GQ1b epitope on HSV-infected human fibroblasts

  VZV

Unclear

  EBV

Molecular mimicry? (anti-GQ1b antibodies);

Vasculitis and neuritis caused by direct invasion

  Hepatitis virus

Molecular mimicry? (anti-GM1 and GM2 antibodies);

Vasculitis and neuritis caused by immune complex accumulation

  Influenza virus

Molecular mimicry between glycoproteins of influenza viruses and glycolipids of peripheral nerves;

Secondary infection

  JEV

Unclear

  HIV

Direct damage to nerves;

Abnormal immunoregulation (formation of anti-sulfatide antibodies against myelin)

  ZIKV

Direct damage to nerves (neurotropism);

Molecular mimicry: peptide sharing between ZIKV proteins and human myelin protein-associated GBS

  SARS-CoV-2

Unclear;

Molecular mimicry? cytokine storm? abnormal activation of T or B cells? direct invasion? complement participation and mediation?

Non-infectious events

 Vaccines

Unclear;

Molecular mimicry? (formation of anti-GM1antibodies induced by influenza vaccines)

 Surgery

Immune dysfunction caused by surgery;

Transient immunosuppression;

Increased risk of secondary infection;

Physical compression of the nerves;

Activation of the endocrine stress systems

 Exogenous gangliosides treatment

Immunogenicity of exogenous ganglioside (producing IgG anti-ganglioside antibodies)

 ICIs

Imbalances in immunologic tolerance;

Molecular mimicry? (shared GM2 and GD3 epitopes between melanoma and myelin sheath)

 Pregnancy

Transient immunosuppression;

Increased risk of opportunistic infections

 SLE

Increased susceptibility to infections;

Humoral immune response: autoantibodies against peripheral nerve myelin in GBS (a part of spectrum of autoantibodies observed in SLE);

More potent response to neurogenic protein

  1. GBS Guillain-Barré syndrome, C. jejuni Campylobacter jejuni, LOS lipooligosaccharide, M. pneumoniae Mycoplasma pneumoniae, H. influenzae Haemophilus influenzae, CMV Cytomegalovirus, HSV Herpes simplex virus, VZV Varicella-zoster virus, EBV Epstein-Barr virus, JEV Japanese encephalitis virus, HIV Human immunodeficiency virus, ZIKV Zika virus, SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2, ICIs immune checkpoint inhibitors; SLE Systemic lupus erythematosus.