Paranodal and other autoantibodies in chronic inflammatory neuropathies

Autoimmune disorders of the peripheral nerves are diverse and heterogeneous. T cells, macrophages, and autoantibodies have been implicated in their pathogenesis. Autoantibodies to peripheral nerve molecules seem to play a role not only in the pathogenesis but provide diagnostic, prognostic, and therapeutic help. We review the state of the art and most relevant recent findings regarding autoantibodies in chronic inflammatory neuropathies, focusing on their clinical utility. Research on autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has received a recent boost with the description of antibodies against proteins of the node of Ranvier. Antibodies of the IgG4 isotype targeting the paranodal proteins contactin-1 (CNTN1) and neurofascin-155 (NF155) define specific CIDP subtypes and have diagnostic and prognostic implications. In multifocal motor neuropathy, anti-GM1 production is restricted to very few B-cell clones that could be the target of therapies aimed to remove or inactivate them. Moreover, novel ELISA and glycoarray techniques combining GM1 and galactocerebroside gangliosides improved the sensitivity of autoantibody detection. Detailed clinical and paraclinical features, including autoantibody reactivity patters, of autoimmune syndromes affecting simultaneously the central and peripheral nervous systems, are also described. The heterogeneity of chronic inflammatory neuropathies is being unraveled with the description of specific autoantibodies and their association with small disease subtypes. The recently described paranodal autoantibodies anti-CNTN1 and NF155 have direct clinical value and seem to determine response to treatment. Further studies are needed to fully understand the primary contribution of the antibodies to the pathophysiology of the immune neuropathies.