Comparative Analytical Performance of Autoimmune Nodopathy Diagnostic Assays.

BACKGROUND: Autoimmune nodopathy (AN) is a disabling peripheral nerve disorder mediated by four pathogenic autoantibodies targeting the node of Ranvier: anti-neurofascin-155 (Nfasc155); anti-Nfasc155 and Nfasc186 (PanNfasc); anti-contactin-1; and anti-contactin-associated protein 1 autoantibodies. Several autoantibody detection assays exist; however, which assay yields the best performance remains unclear. We evaluated the performance of five diagnostic assays individually and in combinations to identify a gold standard assay for diagnosing AN and improve diagnostic accuracy.

METHODS: Sera from 290 individuals from a European cohort, including healthy controls and patients with Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, monoclonal gammopathy, Charcot-Marie-Tooth disease, and AN were tested using five diagnostic assays for AN: ImmunoDOT (D-tek, Mons, Belgium); ELISA; an in-house cell-based assay (CBA); a commercial CBA (Euroimmun, Bussy-Saint-Martin, France); and peripheral nerve immunohistochemistry (IHC). The sensitivity (Se) and specificity (Sp) of the individual assays and their combinations were estimated using Bayesian latent class analysis.

RESULTS: The overall Se was 84% (95% credibility interval [CI], 79-88) for ImmunoDOT, 86% (81-90) for ELISA, 96% (93-98) for the in-house CBA, 92% (89-96) for the commercial CBA, and 91% (87-94) for IHC. For all assays, the overall Sp was ≥ 97%. Among the tested assays, in-house CBA showed the best performance, with the highest Se and Sp. The assay combinations demonstrated excellent analytical performance (Se ≥ 91% and Sp ≥ 98%). Inter-laboratory validation revealed excellent repeatability, with a Gwet's agreement coefficient of >0.94 for most assays.

CONCLUSIONS: Our research suggests that combining two assays, CBA and ImmunoDOT enhances the accuracy of AN diagnosis. This approach can facilitate the establishment of standardized assays for AN diagnosis and aid in the better differentiation of AN from other similar pathologies.