Recent Advances in Structural Basis for Molecular Mimicry in Inflammatory Autoimmune Demyelinating Polyneuropathy - Molecules: Nucleation, Aggregation and Crystallization - page 307

motor axonal neuropathy (AMAN) and acute motor and sensory axonal neu-
ropathy (AMSAN) has been found along with linkages to C. jejuni infection.
Much of the research into GBS over the last decade has focused on the
forms mediated by anti-ganglioside antibodies (Willison, 2005). The iden-
tification of molecular mimicry between GBS associated pathogens, par-
ticularly C. jejuni lipopolysaccharides (LPSs) and GM1, GD1a and GT1a
ganglioside in peripheral nerve tissue, has been investigated from mimic
structural characterization to genetic polymorphism (Godschalk et al ., 2007).
Besides the emerging correlations between anti-ganglioside antibodies and
specific clinical phenotypes, notably between anti-GM1/anti-GD1a antibod-
ies and AMAN, the complexes of different antibodies have also been found
and shown to be reactive in “antibody-negative” GBS sera, i.e. GD1a-GD1b,
GD1b-GT1b (Godschalk et al ., 2007). Despite this rapidly advancing progress
in molecular mimicry of GBS, considerable gaps in our knowledge persist.
MFS is characterized by the acute onset of ophthalmoplegia, ataxia and
flexia, and is the most common variant of GBS with which it often over-
laps clinically, accounting for 5-10% of cases. It is now widely accepted
that well over 90% of patients with MFS have the anti-GQ1b IgG anti-
body, which is completely absent in normal and other disease control groups
(Willison, Yuki, 2002).
A true case of molecular mimicry
Molecular mimicry is one mechanism of GBS by which infectious agents,
most frequently C. jejuni, may trigger an autoimmune response against
myelin or axons, the nerve conduits for signals to and from the brain (Fig. 1).
The mistaken attach is considered to originate from the resemblance
between the microbial LPSs and the ganglioside of human nerve tissues.
It used to be thought that in AIDP the attack appears to be directed against
a component of Schwann cells, while in AMAN the attack appears to be
against the axonal and nodes of Ranvier. However, recent studies have
shown that anti-ganglioside antibodies can: (i) destroy the nerve terminal
(i.e. synaptic necrosis), (ii) kill the perisynaptic Schwann cell (pSC) that
envelops the pre-synaptic region, or (iii) destroy both nerve terminal and
pSC (Halstead et al ., 2005).