Abstract
The important role of B cells and autoantibodies in the pathogenesis of MS is increasingly
appreciated. The recruitment and maintenance of B cells and plasma cells in MS lesions
is presumably based on local production of lymphoid chemokines and B cell activation
factor of the TNF family (BAFF). The failure of the clinical trial with Atacicept
targeting BAFF and its relative APRIL was a great surprise and cannot readily be explained.
A role for BAFF in CNS physiology, e.g. via targeting of the Nogo-66 receptor might
have to be considered. The identification of patient subgroups based on autoantibodies
is a future challenge. Currently patients with neuromyelitis optica (NMO) can be identified
by antibodies to aquaporin 4 and about a third of children with acquired demyelinating
diseases have antibodies against conformationally correct MOG, while such antibodies
are hardly found in adult MS patients. Searching for new targets of the autoimmune
response in adult MS patients, we have identified two axo-glial proteins focused around
the node of Ranvier, namely neurofascin and contactin-2/TAG-1. Testing the functional
relevance of such an autoimmune response in animal models revealed that antibodies
to neurofascin may induce axonal injury and that T cells specific for contactin-2/TAG-1
mediate preferentially gray matter injury.
Keywords
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Article info
Publication history
Published online: September 06, 2010
Accepted:
August 9,
2010
Received in revised form:
August 5,
2010
Received:
May 11,
2010
Footnotes
☆This article is based on a presentation given at the European Charcot Foundation Symposium “Treatment Targets in Multiple Sclerosis”, held in Lisbon, Portugal, November 12–15, 2009.
Identification
Copyright
© 2010 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
