The prevalence of anti-neurofascin-155 antibodies in patients with neuromyelitis optica spectrum disorders

Abstract

Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.

Keywords: anti-neurofascin-155 antibodies; autoimmune diseases; demyelination; neuromyelitis optica spectrum disorders.

FIGURE 1

Detection of anti‐NF155 antibodies by cell‐based assay and immunostaining of teased mouse sciatic nerve fibres. (a) Serum from a representative neuromyelitis optica spectrum disorders (NMOSD) patient with anti‐NF155 antibodies showed reaction with cells expressing human NF155‐GFP. Scale bar = 50 μm. (b) Serum from a representative NMOSD patient with anti‐NF155 antibodies showed co‐localizing with anti‐Caspr antibody in teased mouse sciatic nerve fibres. Scale bar = 10 μm. (c) Single‐staining with serum from anti‐NF155 antibody‐positive NMOSD patients and commercial anti‐Caspr antibodies demonstrated no cross‐reactions. Scale bar = 10 μm. (c) The co‐localizing with paranode was abolished in the serum of anti‐NF155 antibody‐positive NMOSD patients after preincubation with NF155‐transfected HEK 293 cells, but remained in the serum preincubated with non‐transfected HEK 293 cells. Scale bar = 10 μm. NF155 = neurofascin‐155; GFP = green fluorescent protein; HEK = human embryonic kidney; Caspr = contactin‐associated protein

FIGURE 2

Detection of immunoglobulin (Ig) G subclass of anti‐NF155 antibody by cell‐based assay and immunostaining of teased mouse sciatic nerve fibres. (a) A representative IgG1 subclass of anti‐NF155 antibody was detected in a neuromyelitis optica spectrum disorders (NMOSD) patient using a cell‐based assay. Scale bar = 50 μm. (b) A representative IgG1 subclass of anti‐NF155 antibody was confirmed using immunostaining of teased mouse sciatic nerve fibres. Scale bar = 10 μm. NF155 = neurofascin‐155; GFP = green fluorescent protein; Caspr = contactin‐associated protein