Familial Occurrence of Anti-NF155 Autoimmune Nodopathy in Father and Son: Expanding the Spectrum of IgG4-Related Nodopathies.

Abstract

We report the first documented familial occurrence of Anti-Neurofascin-155 (Anti-NF155) autoimmune nodopathy in both a father and his son. Anti-NF155 nodopathy can resemble chronic inflammatory demyelinating polyneuropathy (CIDP) but differs in its poor response to standard CIDP treatments such as intravenous immunoglobulin (IVIG) and steroids, instead requiring B-cell-depleting therapies. A previously healthy 34-year-old male presented with a five-to-six week history of subacute sensory ataxia, symmetric proximal and distal weakness, and areflexia, preceded by right-sided Bell's palsy. Cerebrospinal fluid (CSF) analysis demonstrated albumin-cytologic dissociation with a markedly elevated protein level of 485 mg/dL, and nerve conduction studies confirmed a demyelinating polyneuropathy. Despite treatment with IVIG and corticosteroids, he showed minimal improvement, and subsequent detection of Anti-NF155 antibodies in serum established the diagnosis. He improved significantly with rituximab therapy and was able to walk unassisted at 1-year follow-up. Notably, his 13-year-old son presented with a similar clinical syndrome at the age of 8, characterized by progressive bilateral weakness, sensory ataxia, tremor, elevated CSF protein of 201 mg/dL, diffuse nerve root enhancement on MRI, and demyelinating polyneuropathy on electrophysiologic studies. He was initially treated as CIDP but failed to respond to IVIG and steroids, later testing positive for Anti-NF155 antibodies, and has since achieved sustained improvement on rituximab maintenance every six months. This report emphasizes the possibility of genetic predisposition in the pathogenesis of Anti-NF155 nodopathy and underscores the need for further investigation into familial and environmental factors contributing to disease susceptibility.