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Published January 1, 2019 | Version v1
Journal article Open

Anti-pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy

Creators

  • 1. Ludwig Maximilians Univ Munchen, Dept Neurol, Univ Hosp Wurzburg, Planegg Martinsried, Germany
  • 2. Univ Klinikum Schleswig Holstein, Neuroimmunol Sect, Inst Clin Chem, Campus Kiel, Kiel, Germany
  • 3. Univ Hosp Halle, Dept Neurol, Halle, Germany
  • 4. Univ Hosp Mainz, Dept Neurol, Mainz, Germany
  • 5. Univ Hosp Aachen, Inst Neuropathol, Aachen, Germany
  • 6. Univ Hosp Magdeburg, Dept Neurol, Magdeburg, Germany
  • 7. Univ Hosp Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany
  • 8. Ludwig Maximilians Univ Munchen, Inst Clin Neuroimmunol, Univ Hosp Wurzburg, Biomed Ctr, Planegg Martinsried, Germany
  • 9. Otto Von Guericke Univ, Inst Pharmacol & Toxicol, Magdeburg, Germany

Description

Objective To identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms. Methods Screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays. Results Two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti-NF-155 IgG4 were directed against the NF-155-specific Fn3Fn4 domain. The description of a second phenotype of anti-NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year. Conclusions Our results indicate that anti-pan-NF-associated neuropathy differs from anti-NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti-NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.

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