Antibodies for Nodal and Paranodal Syndromes: Serum Testing
Antibodies for nodal and paranodal syndromes are found in serum, not cerebrospinal fluid (CSF). These antibodies target proteins at the node of Ranvier and paranodal regions of peripheral nerves, making them distinct from central nervous system neuronal surface antibodies where both serum and CSF testing may be relevant.
Key Diagnostic Considerations
Primary Testing Site
- Serum is the appropriate specimen for detecting nodal/paranodal antibodies including anti-neurofascin 186 (NF186), anti-neurofascin 155 (NF155), anti-contactin-1 (CNTN1), and anti-contactin-associated protein-1 (Caspr1) 1, 2
- These antibodies target peripheral nerve structures, not CNS antigens, which explains why serum rather than CSF is the diagnostic fluid of choice 3, 4
Distinction from CNS Antibody Syndromes
- This contrasts sharply with CNS neuronal surface antibody syndromes (such as anti-NMDAR encephalitis), where both serum and CSF should be tested when possible 5, 6
- The gold standard for CNS neuronal surface antibody detection involves testing patient serum diluted 1:10 or greater, or CSF usually diluted from 1:1 to 1:10 5
- Serial estimations of antibody levels in serum and CSF can be helpful for monitoring CNS antibody-mediated conditions 5
Clinical Context
Autoimmune Nodopathies
- Nodal/paranodal antibodies are detected in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome variants 1, 4
- In one cohort, 10.6% had IgG against NF155, 6.4% against Caspr1, 4.3% against NF186, and 2.1% against CNTN1 1
- These antibodies are predominantly of the IgG4 subclass during chronic phase, though complement-fixing IgG3 antibodies are detected during early aggressive phases 4, 7
Pathophysiology
- IgG4 anti-paranodal protein antibodies primarily block protein-protein interactions between NF155 and CNTN1/Caspr1, leading to conduction failure 3
- Sural nerve pathology shows paranodal terminal loop detachment from axons with intact internodes in the absence of inflammation 3
Treatment Implications
- Recognition of these serum antibodies is crucial because patients often respond poorly to conventional immunomodulatory therapies like intravenous immunoglobulin (IVIG) 2, 4
- B cell depleting therapies such as rituximab have been reported to significantly improve functional outcomes, with effectiveness rates of 75% in antibody-positive patients 1, 7