Chapter 20
Guillain Barré-Syndrome
Helmar C. Lehmann and Kazim A. Sheikh
QUESTIONS
1.
What is meant by the term molecular mimicry?
2.
What is the basis of hypothesis of molecular mimicry in the pathogenesis of GBS?
3.
What are the potential mechanisms of antibody-mediated peripheral nerve dysfunction/injury?
4.
What are the potential mechanisms of T-cell mediated peripheral nerve dysfunction/injury?
20. Guillain Barré-Syndrome
Helmar C. Lehmann and Kazim A. Sheikh
2
Answers
1. What is meant by the term molecular mimicry?
The term molecular mimicry describes a mechanism whereby epitopes incidentally shared by microbial
antigens and nerve structures elicit an autoreactive T- or B-cell response in the wake of an infective illness.
2.
What is the basis of hypothesis of molecular mimicry in the pathogenesis of GBS?
In GBS there is clinical and experimental evidence that molecular mimicry is an important mechanism how
an autoimmune response against peripheral nerve tissue is induced. Several observations support this
hypothesis: Epidemiological studies have established a relationship between Campylobacter jejuni and the
occurrence of Guillain-Barré Syndrome. GBS-patients with antecedent C. jejuni infection frequently
associate with an axonal subtype of GBS called acute axonal motor neuropathy (AMAN). Cases of AMAN
are significantly associated with the presence of antibodies against the gangliosides GD1a and GM1. C.
jejuni strains isolated from patients with AMAN bear lipo-oligosaccharides on the cell-surface which share
identical chemical structures like the tetrasaccharide structure of GD1a and GM1. The strongest evidence
arises from animal models of AMAN in which immunization with relevant gangliosides or C. jejuni LPS
reproduces clinical and pathological features of AMAN.
3.
What are the potential mechanisms of antibody-mediated peripheral nerve dysfunction/injury?
Experimental evidence suggests that a variety of effects are produced by antibodies on peripheral nerve. For
example studies indicate that anti-GM1 antibodies may block or alter channel function. Alternatively,
Willison and colleagues demonstrated on ex vivo phrenic nerve-diaphragm preparation, that anti-GQ1b and
anti-GD1a antibodies bind to nerve terminals, cause complement-dependent quantal acetylcholine (ACh)
release, which results in neuromuscular blockade. In patch-clamp experiments IgG GQ1b, GD1a, GD1b and
GM1 antibodies have been shown to cause reversible complement independent pre- and post-synaptic
blockade depending upon the antibody used.
4.
What are the potential mechanisms of T-cell mediated peripheral nerve dysfunction/injury?
Potential mechanisms of T-cell mediated peripheral nerve injury include direct mechanisms like release of
toxic cytokines such as interferon-gamma and tumor necrosis factor-alpha. Both have proinflammatory
effects and mediate myelin damage through activation of macrophages. Furthermore, blood-derived neural
antigen-specific T-cells become reactivated in the PNS, expand clonally and release cytokines to orchestrate
and perpetuate the immune response. The crucial role of T-cells is proven by the adoptive-transfer EAN,
which means the transfer from lymph node cells from animals that had been immunized with myelin induces
demyelinating peripheral nerve injury.