Antibodies to Contactin-1 and Neurofascin 155 (Nfasc155) have recently been associated with subsets of patients with chronic inflammatory demyelinating
polyneuropathy (
CIDP). Contactin-1 and Nfasc155 are
cell adhesion molecules that constitute the septate-like junctions observed by electron microscopy in the paranodes of myelinated axons.
Antibodies to Contactin-1 have been shown to affect the localization of paranodal
proteins both in patient nerve biopsies and in animal models after passive transfer. However, it is unclear whether these
antibodies alter the paranodal ultrastructure. We examined by electron microscopy sural nerve biopsies from two patients presenting with anti-Nfasc155
antibodies, and also four patients lacking
antibodies, three normal controls, and five patients with other neuropathies. We found that patients with anti-Nfasc155
antibodies presented a selective loss of the septate-like junctions at all paranodes examined. Further, cellular processes penetrated into the expanded spaces between the paranodal myelin loops and the axolemma in these patients. These patients presented with important nerve conduction slowing and
demyelination. Also, the reactivity of anti-Nfasc155
antibodies from these patients was abolished in neurofascin-deficient mice, confirming that the
antibodies specifically target paranodal
proteins. Our data indicate that anti-Nfasc155 destabilizes the paranodal axo-glial junctions and may participate in conduction deterioration.