Comparative Analytical Performance of Autoimmune Nodopathy Diagnostic Assays

Area of Science:

• Neurology
• Immunology
• Diagnostic Assay Development

Background:

• Autoimmune nodopathy (AN) is a peripheral nerve disorder caused by autoantibodies targeting the node of Ranvier.
• Key autoantibodies include anti-neurofascin-155 (Nfasc155), anti-Nfasc155 and Nfasc186 (PanNfasc), anti-contactin-1, and anti-contactin-associated protein 1.
• The optimal diagnostic assay for AN remains undetermined.

Purpose of the Study:

• To evaluate the performance of five diagnostic assays for Autoimmune Nodopathy (AN).
• To identify the gold standard assay for diagnosing AN.
• To improve diagnostic accuracy for AN through assay evaluation and combination.

Main Methods:

• Sera from 290 individuals (including AN patients and controls) were tested using five assays: ImmunoDOT, ELISA, in-house cell-based assay (CBA), commercial CBA, and immunohistochemistry (IHC).
• Assay sensitivity (Se) and specificity (Sp) were estimated using Bayesian latent class analysis.
• Assay combinations were also evaluated for diagnostic performance.

Main Results:

• The in-house CBA demonstrated the highest sensitivity (96%) and specificity (≥97%).
• Assay combinations achieved excellent performance, with Se ≥ 91% and Sp ≥ 98%.
• Inter-laboratory validation showed high repeatability (Gwet's agreement coefficient >0.94).

Conclusions:

• Combining cell-based assays (CBA) and ImmunoDOT significantly enhances AN diagnostic accuracy.
• This combined approach facilitates standardized AN diagnosis and differentiation from similar neuropathies.
• The study provides a pathway for establishing reliable diagnostic standards for autoimmune nodopathy.