What is the etiology of Acute Inflammatory Demyelinating Polyneuropathy (AIDP), or Guillain-Barré Syndrome?

Etiology of Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

AIDP (the most common form of Guillain-Barré Syndrome) is primarily caused by an autoimmune response triggered by preceding infections, with molecular mimicry between infectious agents and peripheral nerve components being the key pathophysiological mechanism. 1

Infectious Triggers

• Approximately two-thirds of patients with GBS report symptoms of an infectious disease within 4 weeks preceding the onset of weakness 1
• Upper respiratory tract infections are the most common antecedent events (22-53% of cases) in Europe, North America, South America, and parts of Asia 1
• Respiratory infections are even more common in pediatric GBS cases (50-70%) 1
• In some regions like India and Bangladesh, gastroenteritis is the most frequent preceding event (36-47%) 1

Specific Infectious Agents Associated with AIDP:

• Viral agents:

  • Cytomegalovirus 2, 3
  • Epstein-Barr virus 2, 3
  • Zika virus (associated with GBS outbreaks in French Polynesia and Latin America) 1, 4
  • Hepatitis E virus (particularly in children) 1

• Bacterial agents:

  • Campylobacter jejuni (most frequently identified trigger worldwide, 30-32% of cases in most regions, up to 60-70% in some areas) 1, 5
  • Mycoplasma pneumoniae 2, 3
  • Haemophilus influenzae 3

Pathophysiological Mechanism

• Molecular mimicry: The primary mechanism involves structural similarities between microbial components and peripheral nerve tissues 1, 5

  • In AIDP specifically, immune reactions target epitopes in Schwann cells or myelin, resulting in demyelination 2
  • The exact target molecules in AIDP have not been fully identified, unlike in AMAN where gangliosides are well-established targets 2, 5

• Immune response: The infection triggers an autoimmune response that causes demyelination and axonal degeneration of peripheral nerves and nerve roots 1

  • Cross-reactive antibodies develop against myelin components 3
  • Complement activation plays a role in nerve damage 2

Geographic Distribution and Variant Correlation

• AIDP is the most common subtype in Europe and North America (83-90% of GBS cases) 1, 2
• In Asia, AIDP remains common but with regional variations (34-80% of GBS cases) 1
• In regions where AMAN is the predominant variant, AIDP still accounts for 22-46% of cases 1
• The distribution of GBS subtypes correlates with the prevalence of specific infectious triggers in different regions 1

Non-Infectious Triggers

• Vaccines and immunomodulatory agents: Rarely associated with GBS development 1
• Other events: Surgery and malignancy have been temporally related to GBS, though the underlying mechanisms remain unclear 1

Host Factors

• Genetic factors: Polymorphisms in genes like TNF (tumor necrosis factor) and MBL2 (mannose-binding protein C) have been associated with GBS susceptibility 1
• Nutritional status: Poor nutritional status and malnutrition may alter immune responses implicated in GBS pathogenesis 1
• Individual susceptibility: Despite widespread exposure to triggering infections, only a small fraction develop GBS (e.g., only 1 in 1,000-5,000 patients with C. jejuni infection develop GBS) 1

Clinical Implications

• The specific infectious trigger may influence disease severity and prognosis 3
• C. jejuni-associated GBS tends to be more severe than GBS due to other causes 5
• In countries where C. jejuni infection is more common, approximately 80% of patients present with severe GBS (disability score >2) compared to 40-60% in regions where AIDP is more prevalent 1