Intrathecal Antibody Synthesis in Autoimmune Nodopathy

Background

Autoimmune nodopathy (AN) is caused by autoantibodies targeting the nodes of Ranvier or paranodes. AN frequently affects cranial nerves and spinal nerve roots and may accompany central demyelination, all of which belong to the intrathecal compartment. We aimed to ascertain the frequency of intrathecal antibody synthesis and blood–CSF barrier (BCSFB) dysfunction in AN and their clinical correlates.

Methods

We analyzed paired cerebrospinal fluid (CSF) and serum samples from 110 patients with AN, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and Guillain-Barré syndrome (GBS). BCSFB dysfunction and intrathecal total IgG synthesis were assessed using Q_Alb, Q_IgG-total, and IgG index. Flow cytometry was used to evaluate intrathecal autoantibody synthesis.

Results

Compared to CIDP and GBS, AN patients more frequently exhibited BCSFB dysfunction (87.5%) and intrathecal total IgG synthesis (68.8%). Among AN patients with cranial nerve or brain involvement (8/16, 50%), all had either an elevated IgG index (n = 7) or CSF-specific oligoclonal bands (n = 1). Intrathecal autoantibody synthesis was confirmed in 2 patients. Notably, both patients initially presented with cranial neuropathies. No CSF-restricted AN autoantibodies were found in the 39 seronegative CIDP and GBS patients.

Conclusions

AN exhibits distinct immunopathogenesis compared to CIDP and GBS. Intrathecal synthesis of total IgG is associated with cranial nerve or central nervous system involvement, while that of AN-specific autoantibodies relates to cranial nerve onset diseases.