A Next-Generation ELISA for the Detection of Anti-(Para)Nodal Antibodies in Autoimmune Nodopathy and COVID-19 Vaccinated Individuals.

BACKGROUND AND AIMS: Autoimmune nodopathy (AN) is a subtype of antibody-mediated inflammatory neuropathy targeting the node of Ranvier (NoR). Diagnosis requires detection of anti-(para)nodal autoantibodies like contactin-1 and neurofascin-155 via ELISA or cell-based assays, but protocols are inconsistent. Causes of node autoimmunity are unknown, and respiratory infections, including SARS-CoV-2 infection or COVID-19 vaccination as triggers, have not been thoroughly investigated. We aim to establish and validate a next-generation automated ELISA for anti-(para)nodal antibodies and investigate whether low-titer antibodies occur in recently COVID-19-vaccinated healthy individuals. METHODS: We used the Ella platform to customize an automated ELISA for anti-contactin-1, -neurofascin-155, and -Caspr-1 serum IgG. Patients with known AN (23 anti-neurofascin, 13 anti-contactin-1, and 8 anti-Caspr-1), 64 patients with seronegative (sub) acute inflammatory neuropathies, and 30 healthy controls served for validation, including quality analysis versus standard ELISA. Thirty-seven diagnostic samples of patients with suspected AN and 280 sera of healthcare workers included in the CoVacSer study, collected 3 weeks after COVID-19 vaccination or infection, were tested for anti-contactin-1 and anti-neurofascin-155. RESULTS: The automated ELISA showed high sensitivity (87.5%-100%) and specificity (98.4%-100%) for identifying AN, with reduced hands-on time, high automation, and similar quality and titer characteristics as standard ELISA. Low-titer anti-neurofascin-155, but no anti-contactin-1 autoantibodies, were detected in 1/280 post-SARS-CoV-2-vaccination or infection sera (0.36%). Longitudinal testing and clinical assessment did not indicate SARS-CoV-2-related neurological symptoms. INTERPRETATION: We provide a highly automated, rapid, universally applicable test platform for anti-(para)nodal antibodies. The low frequency of anti-(para)nodal antibodies and absence of clinical AN manifestations in COVID-19-vaccinated individuals support vaccination safety regarding AN development.