Mechanism of Campylobacter-Induced Guillain-Barré Syndrome
Campylobacter jejuni causes Guillain-Barré syndrome through molecular mimicry, where structural similarities between bacterial surface lipooligosaccharides and human peripheral nerve gangliosides trigger cross-reactive antibodies that attack the nervous system. 1, 2
The Molecular Mimicry Mechanism
The pathogenesis centers on a case of mistaken identity by the immune system:
C. jejuni expresses lipooligosaccharides (LOS) on its cell surface that structurally mimic human nerve gangliosides (specifically GM1, GM1b, GD1a, and GalNAc-GD1a), creating the molecular basis for autoimmune attack 1, 2
These bacterial surface components are sufficiently similar to peripheral nerve structures that antibodies generated against the bacteria cross-react with nerve tissue, activating complement and causing direct nerve damage 1, 3
The cross-reactive antibodies target either myelin (causing demyelinating forms like AIDP) or axons directly (causing axonal forms like AMAN), with C. jejuni being associated with both pathologic subtypes 2, 3
Why Only Some Infected Patients Develop GBS
Despite C. jejuni being the most common bacterial cause of gastroenteritis, GBS remains rare:
Only 1 in 1,000-5,000 patients with C. jejuni infection develop GBS within the subsequent 2 months, highlighting that infection alone is insufficient 4, 5
Not all C. jejuni strains possess the carbohydrate mimicry structures required to trigger cross-reactive antibodies—this strain-specific variation is a critical determinant 4, 5
Host genetic factors significantly influence susceptibility, particularly polymorphisms in the TNF gene (encoding tumor necrosis factor) and MBL2 gene (encoding mannose-binding protein C) that affect immune response activation 4, 5
Intrinsic dendritic cell responsiveness to C. jejuni LOS through Toll-like receptor 4 (TLR4) activation determines disease susceptibility—patients who develop GBS demonstrate significantly higher DC responses with increased CD38 and CD40 expression compared to controls 6
Geographic and Clinical Patterns
The C. jejuni-GBS relationship shows important regional variations:
C. jejuni accounts for 30-32% of GBS cases globally, but reaches 60-70% in certain regions like Curaçao, China, and Bangladesh where the organism is particularly prevalent 1, 5
In regions with high C. jejuni prevalence, approximately 80% of patients present with severe GBS (disability score >2) compared to 40-60% in regions where demyelinating forms predominate, suggesting C. jejuni-associated cases tend toward greater severity 1, 5
Axonal subtypes following C. jejuni infection are more common in Asia and may be more severe than the demyelinating forms that predominate in Europe and North America 1, 3
Critical Pitfalls
When evaluating the C. jejuni-GBS connection, avoid these common errors:
Do not assume all GBS following gastroenteritis is C. jejuni-related—other pathogens and even viral respiratory infections can trigger GBS, with respiratory infections being the most common antecedent event (22-53%) in many regions 1, 5
The temporal relationship matters: GBS typically develops 3-30 days after the infectious illness, with most patients reaching maximum disability within 2 weeks of neurologic symptom onset 4, 1
Not all C. jejuni serotypes carry equal risk—specific serotypes like Lior 11 have been associated with GBS, while the most common enteritis-causing serotype (Lior 4) may not 7