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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Pathol
2012 ; 181
(4
): 1402-13
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Antibodies to gliomedin cause peripheral demyelinating neuropathy and the
dismantling of the nodes of Ranvier
#MMPMID22885108
Devaux JJ
Am J Pathol
2012[Oct]; 181
(4
): 1402-13
PMID22885108
show ga
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating
polyneuropathy (CIDP) are conditions that affect peripheral nerves. The
mechanisms that underlie demyelination in these neuropathies are unknown.
Recently, we demonstrated that the node of Ranvier is the primary site of the
immune attack in patients with GBS and CIDP. In particular, GBS patients have
antibodies against gliomedin and neurofascin, two adhesion molecules that play a
crucial role in the formation of nodes of Ranvier. We demonstrate that immunity
toward gliomedin, but not neurofascin, induced a progressive neuropathy in Lewis
rats characterized by conduction defects and demyelination in spinal nerves. The
clinical symptoms closely followed the titers of anti-gliomedin IgG and were
associated with an important deposition of IgG at nodes. Furthermore, passive
transfer of antigliomedin IgG induced a severe demyelinating condition and
conduction loss. In both active and passive models, the immune attack at nodes
occasioned the loss of the nodal clusters for gliomedin, neurofascin-186, and
voltage-gated sodium channels. These results indicate that primary immune
reaction against gliomedin, a peripheral nervous system adhesion molecule, can be
responsible for the initiation or progression of the demyelinating form of GBS.
Furthermore, these autoantibodies affect saltatory propagation by dismantling
nodal organization and sodium channel clusters. Antibodies reactive against nodal
adhesion molecules thus likely participate in the pathologic process of GBS and
CIDP.