Clinical Features of Autoimmune Nodopathy With Anti-Neurofascin-155 Antibodies in South Koreans

Abstract

Background and purpose: Anti-neurofascin-155 (NF155) antibody is one of the autoantibodies associated with autoimmune nodopathy. We aimed to determine the clinical features of South Korean patients with anti-NF155-antibody-positive autoimmune nodopathy.

Methods: The sera of 68 patients who fulfilled the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) were tested for anti-NF155 antibodies using a cell-based assay (CBA) and enzyme-linked immunosorbent assay (ELISA). The anti-NF155-positive sera were also assayed for NF155 immunoglobulin G (IgG) subclasses, and for anti-NF186 and NF140 antibodies. The clinical features of the patients were reviewed retrospectively.

Results: Among the 68 patients, 6 (8.8%) were positive for anti-NF155 antibodies in both the CBA and ELISA. One of those six patients was also positive for anti-NF186 and anti-NF140 antibodies. IgG4 was the predominant subclass in four patients. The mean age at onset was 32.2 years. All six positive patients presented with progressive sensory ataxia. Five patients treated using corticosteroids presented a partial or no response. All six patients were treated using intravenous immunoglobulin (IVIg). Among them, five exhibited a partial or poor response and the other exhibited a good response. All three patients treated using rituximab showed a good response.

Conclusions: The clinical characteristics of the patients were consistent with those in previous studies. Anti-NF155 antibody assay is necessary for diagnosing autoimmune nodopathy and its appropriate treatment, especially in young patients with CIDP who present with sensory ataxia and poor therapeutic responses to corticosteroids and IVIg.

Keywords: autoantibodies; autoimmune diseases; neurofascin; nodes of Ranvier; peripheral neuropathy.

Fig. 1. Results from cell-based assays with human recombinant NF155-transfected HEK293 cells. HEK293 cells that expressed NF155 were incubated using (A) commercially available polyclonal anti-NF155 antibodies, (B) serum from patient 1, and (C) serum from a healthy control. A and B: Alexa-Fluor-594-conjugated anti-IgG antibody binding was observed along the cell surface (red fluorescence). This was colocalized with GFP-labeled NF155 expressed on the HEK293 cells (green fluorescence), indicating the presence of anti-NF155 antibodies. C: Antihuman IgG antibody binding (red fluorescence) was not observed when the serum from the healthy control was applied. DAPI, 4′,6-diamidino-2-phenylindole; GFP, green fluorescent protein; HEK293, human embryonic kidney 293; IgG, immunoglobulin G; NF, neurofascin.

Fig. 2. Reactivity to anti-NF antibodies in the ELISA. A: Serum samples from patients who fulfilled the CIDP diagnostic criteria (n=68), controls with disease (n=20), and healthy controls (n=12) were tested for anti-NF155 IgG autoantibodies. The line represents the mean OD of healthy controls plus 5 standard deviations. B: IgG subclass was evaluated in patients with anti-NF155 seropositivity. C and D: Anti-NF186 and anti-NF140 autoantibodies were examined in the sera of controls and those with anti-NF155 positivity. The line represents the mean OD of healthy controls plus 5 standard deviations. CIDP, chronic inflammatory demyelinating polyneuropathy; IgG, immunoglobulin G; NF, neurofascin; OD, optical density.

Fig. 3. Clinical status and anti-NF155 titers in patient 2. After treatment with plasma exchange and rituximab, the mRS score improved and anti-NF155 antibody titers decreased. Titer variation within patient 2 was expressed as the percentage titer change relative to baseline levels. IV, intravenous; mRS, modified Rankin Scale; NF, neurofascin.