Chronic Inflammatory Demyelinating Polyradiculoneuropathy/Autoimmune Nodopathy (CIDP) Profile

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a type of chronic autoimmune neuropathy characterized by myelin damage, leading to issues with nerve conduction and excitability. Since its identification, the exact antigenic target of CIDP remains unknown in most cases, making it challenging to correlate electrophysiological findings with the disease's pathophysiology and clinical presentation. Affecting approximately two to four individuals per 100,000, CIDP is a rare cause of polyneuropathy, but accurate diagnosis is essential as it can be effectively treated with immunomodulating therapies. The precise immune trigger for CIDP is still unclear, though some patients suspected of having CIDP have been found to carry autoantibodies against nodal-paranodal proteins. These patients often exhibit distinct immunopathological mechanisms, clinical symptoms and treatment responses compared to those with classic CIDP. Recognizing these differences is crucial for personalizing treatment and improving patient outcomes. 

Autoantibodies targeting nodal and paranodal structures have shown significant pathophysiological importance and have become clinically useful biomarkers. In recent years, specific CIDP biomarkers have been identified, including antibodies against the node of Ranvier and paranodal proteins such as anti-neurofascin (NF)155, anti-contactin-1 (CNTN1), anti-NF186 and anti-contactin- associated protein 1 (CASPR1). NF155 is located at the paranodal loops of Schwann cells, where it interacts with CNTN1 on neighboring axons to stabilize the paranodal axoglial junction. Animal models show that disrupting this interaction with antibodies mimics the pathophysiology seen in humans. Approximately 5% to 10% of patients with CIDP-like symptoms have NF155 IgG antibodies, which are less common in more acute forms of demyelinating polyradiculoneuropathy. CNTN1 IgG antibodies are present in about 2% of patients with CIDP-like symptoms. Patients with CNTN1 IgG positivity are more likely to experience neuropathic pain, sensory ataxia and subacute progressive demyelinating polyradiculoneuropathy or polyradiculopathy. 

NF186 IgG seropositivity is associated with polyradiculopathy or radiculoplexus neuropathy phenotypes, with most seropositive patients showing significant respiratory dysfunction, disproportionate to most acquired polyradiculoneuropathies. CASPR1, a cell-adhesion protein expressed by neurons, forms a complex with CNTN1, which binds to the glial protein NF155. Together, they create septate-like junctions (transverse bands) that connect the paranodal loops of Schwann cells to the axon at the paranode. In patients with CASPR1 antibodies, sensory nerve symptoms are more pronounced than motor symptoms, and nerve conduction tests often yield positive results. Anti-Caspr1/CNTN1 complex autoantibodies are associated with a rapidly progressing form of CIDP that involves cranial nerves, early axonal damage, and a poor response to IVIg therapy. These antibodies primarily target CASPR1, but their binding is stronger when CNTN1 is also present. The European Academy of Neurology and the Peripheral Nerve Society recommend testing for anti-MAG antibodies in all patients with an IgM paraprotein who meet the diagnostic criteria for CIDP, particularly in cases of distal CIDP. Anti-MAG antibodies are particularly relevant when associated with a distal CIDP phenotype and the presence of an IgM paraprotein.