Antibodies to nodal/paranodal proteins in paediatric immune-mediated neuropathy

Background: The identification of autoantibodies against epitopes at the node of Ranvier in peripheral immune-mediated neuropathies has led to new insights and therapeutic implications in Guillain-Barré-syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Their relevance in pediatric immune-mediated neuropathies is unclear.

Objective: To report clinical features and frequency of nodal/paranodal antibodies in a cohort of 54 pediatric patients with immune-mediated neuropathy.

Methods: We reviewed clinical and paraclinical data of 54 children with GBS (n=42) and CIDP (n=12) that were referred to our center for autoantibody testing from hospitals in Germany, Austria, and Croatia between 2006 and 2018. All serum samples were screened for autoantibodies against neurofascin155 (NF155), NF186, NF140, contactin-1 (CNTN1), contactin-associated protein1 (CASPR1), and gangliosides (GM1, GD1a, GD1b, GQ1b) using tissue- and cell-based assays, and ELISAs.

Results: Five/12 children with CIDP but none of the 42 GBS patients had nodal/paranodal antibodies: 2 pan-neurofascin (NF155/NF186/NF140 triple-positive), 1 NF155, and 2 CNTN1-antibodies. Mean age was 7.9 years (range 3-11), the male:female ratio was 3:2. Median duration of hospitalization was 13 days (range 2-28). One child had an acute onset, the other four a prolonged atypical disease course. All children had ataxia, four neuropathic pain (all except 1 panneurofascin) and three (2 CNTN1, 1 pan-neurofascin) tremor. One had a preceding infection. At peak of disease, three children needed a walking aid (Hughes 3) and two were bedridden (Hughes 4). Three/5 patients significantly improved after rituximab treatment, whereas none of the children sufficiently responded to IVIG, steroids and/or plasma exchange.

Conclusion: Paranodal antibodies need to be taken into account in the diagnostic work-up of children with CIDP and atypical/prolonged disease course with high Hughes score (>2), sensory ataxia, prominent neuropathic pain, and tremor, in which IVIG may be insufficient and patients may benefit from rituximab.