Septin multimer autoantibodies in severe motor neuropathy mimicking lower motor neuron disease - PubMed
5 hours ago
- #Autoantibody
- #Septin Multimers
- #Motor Neuropathy
- A novel autoantibody against septin multimers was identified in a severe motor neuropathy mimicking lower motor neuron disease (LMND).
- Three patients diagnosed with the LMND variant of amyotrophic lateral sclerosis tested positive among 3,543 samples, showing a distinct binding pattern on peripheral nerves targeting Schmidt-Lanterman incisures, paranodes, and abaxonal myelin.
- Autoantibody binding was observed in living myelinated dorsal root ganglia, primarily at SLIs (incisuropathy), and initiated complement deposition in cell-based assays.
- Histopathological analysis revealed inflammation, myelin, and axonal pathology in nerve and skin biopsies from one patient.
- Immunotherapy in one patient led to disease stabilization over three years, while two untreated or ineffectively treated patients died from rapid progression.
- Screening for septin multimer autoantibodies is recommended in severe motor-predominant neuropathies resembling LMND due to potential autoimmune causes.
- Further studies are needed to confirm pathogenicity, biomarker potential, and immunotherapy responses in larger cohorts.