Anti‐neurofascin 155 antibody‐related neuropathy

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an intractable inflammatory disease affecting peripheral nerves. The etiology of CIDP remains to be established, but it is regarded as a mixture of heterogeneous conditions presenting a variety of clinical and electrophysiological manifestations. In recent years, autoantibodies against paranodal cell adhesion molecules, such as neurofascin 155 (NF155), contactin 1 and contactin‐associated protein 1, have been detected in subsets of CIDP patients. The clinical characteristics of anti‐NF155 antibody‐positive CIDP have been delineated, and include a younger onset age, higher frequency of distal muscle weakness, sensory ataxia and tremor, higher cerebrospinal fluid protein levels, more conspicuous demyelination on nerve conduction studies, and nerve root hypertrophy on magnetic resonance neurography, when compared with anti‐NF155 antibody‐negative CIDP patients. Predominant elevation of immunoglobulin G4 subclass is also a characteristic of this disease. Sural nerve biopsy specimens of anti‐NF155 antibody‐positive CIDP patients show axo‐glial detachment in paranodes without inflammatory cell infiltrates or onion bulb formation. While intravenous immunoglobulin is not as effective as expected against anti‐NF155 antibody‐positive CIDP patients, other immunotherapies, such as corticosteroids, plasmapheresis and B‐cell depletion therapy, seem to be effective. Early diagnosis and treatment is important for preventing secondary axonal degeneration. The present review summarizes the emerging details of anti‐NF155 antibody‐related neuropathy.

Nerve biopsy: Current indications and decision tools

“…This condition is distinguished from paranodopathies, which are mediated by autoantibodies (predominantly IgG4) against paranodal antigens such as neurofascin‐155 and contactin‐1 88 and are not characterized by IgG4 plasma cell infiltration. 89 …”

“…87 This condition is distinguished from paranodopathies, which are mediated by autoantibodies (predominantly IgG4) against paranodal antigens such as neurofascin-155 and contactin-1 88 and are not characterized by IgG4 plasma cell infiltration. 89 The context of raised serum IgG4 levels and the presence of IgG4 related disease in other organs suggests the diagnosis but definitive diagnosis requires the presence of IgG4-positive plasma cell infiltrates on nerve biopsy. 87 Five cases [90][91][92][93][94] of peripheral neuropathy attributed to IgG4 related disease have been reported although the condition may be under-diagnosed.…”

Aggressive Acquired Demyelinating Neuropathy Caused by NF-155: Initially Treatment-Resistant

“…3 NF-155 has also been reported in combined CIDP and central demyelination, although our patient did not show evidence of this. 4 Typical features of NF-155 cases include sensory ataxia, tremor, and varying degrees of bilateral upper and/or lower limb weakness, although often with more distal than proximal involvement. 5 Although there has been a suggestion that disease severity may be dependent on antibody titers (our patient underwent qualitative testing at Mayo Laboratories), there are case reports describing more aggressive presentations almost uniformly in younger patients (typically aged 18–26 years).…”

An Atypical and Multifactorial Acute Immune Polyradiculopathy: A Case Report

“…Initially identified in the context of multiple sclerosis, 4 antibodies against NF, specifically NF-155, have been associated with a severe and treatmentresistant subset of CIDP. 5 The causal relationship between NF-155 antibodies and demyelinating neuropathy has not been established, but in NF-155 antibody-positive CIDP, NF-155 antibody titers correlate with disease severity 6 and electrodiagnostic impairment 7,8 and predict response to treatment. 9 Clinically, CIDP associated with NF-155 antibodies is more likely to present with a sensory ataxia, 10 tremor, 5,10,11 and hypertrophy of cervical and lumbosacral nerve roots 12 with CSF protein levels greater than 100 mg/dL (mean: 300 mg/dL).…”

“…5 The causal relationship between NF-155 antibodies and demyelinating neuropathy has not been established, but in NF-155 antibody-positive CIDP, NF-155 antibody titers correlate with disease severity 6 and electrodiagnostic impairment 7,8 and predict response to treatment. 9 Clinically, CIDP associated with NF-155 antibodies is more likely to present with a sensory ataxia, 10 tremor, 5,10,11 and hypertrophy of cervical and lumbosacral nerve roots 12 with CSF protein levels greater than 100 mg/dL (mean: 300 mg/dL). 11,12 These patients are more likely to respond to steroids or other immunomodulatory drugs, such as rituximab, and are less likely to respond to intravenous immunoglobulin.…”