Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy
Brain. 2017-05-28; 140(7): 1851-1858
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Chronic inflammatory demyelination polyneuropathy is a heterogeneous and
treatable immune-mediated disorder that lacks biomarkers to support diagnosis.
Recent evidence indicates that paranodal proteins (contactin 1,
contactin-associated protein 1, and neurofascin-155) are the targets of
autoantibodies in subsets of patients showing distinct clinical presentations.
Here, we identified neurofascin-186 and neurofascin-140 as the main targets of
autoantibodies in five patients presenting IgG reactivity against the nodes of
Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient
presented IgG3 antibodies that activated the complement pathway in vitro. These
patients present distinct clinical features compared to those with
anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with
conduction block or decreased distal motor amplitude. Four patients had a
subacute-onset and sensory ataxia. Two patients presented with nephrotic
syndromes and one patient with an IgG4-related retroperitoneal fibrosis.
Intravenous immunoglobulin and corticosteroids were effective in three patients,
and one patient remitted following rituximab treatment. Clinical remission was
associated with autoantibody depletion and with recovery of conduction block and
distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that
the pathogenic mechanisms responsible for chronic inflammatory demyelination
polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in
a subgroup of patients.