Comparison of Commercial Tests for Detecting Multiple Anti-Ganglioside Autoantibodies in Patients with Well-Characterized Immune-Mediated Peripheral Neuropathies

Background: To assess the performance of commercial anti-ganglioside antibody assays, we determined anti-ganglioside antibody IgG and IgM isotype profiles of patients with acute and chronic well-characterized immune-mediated peripheral neuropathies by one immunodot assays (Zentec/Ingen: Dotzen (R) Ganglio Profile Ab, Euroimmun/BioAdvance: Euroline ganglioprofile), two line-immuno assay (GA Generic Assays/Labodia: Anti-Gangliosid Dot, Euroimmun/BioAdvance: Euroline ganglioprofile), and one enzyme-linked immunosorbent assay (ELISA) (Buhlmann: GanglioCombi (R)). Specific antibody profiles were compared with those obtained by our validated standard in-house immunodot assay (IDA). Methods: We selected 33 sera with high levels of IgG and IgM anti-ganglioside antibodies from 15 patients with Guillain-Barre syndrome (GBS) subtypes and variants, 12 patients with CANOMAD syndrome (chronic ataxic neuropathy with ophthalmoplegia, M-paraprotein, cold agglutinins, disialosyl antibodies), 5 patients with chronic motor peripheral neuropathies, and 1 patient with sensory neuropathy and a control group composed of 10 patients with non-autoimmune neuropathy. Results: The 3 commercial IDAs employing hydrophobic membranes and the ELISA demonstrated different carbohydrate epitopes on 6 to 12 glycolipid antigens used for anti-ganglioside antibody detection. Comparison with the validated in-house IDA showed large variations in sensitivity between tests and a more diverse reactivity to gangliosides than expected. The test with the largest panel of glycolipids detecting 11 anti-ganglioside antibody reactivities (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b, and sulfatide) revealed the best concordance with our in-house assay. However, even with this test, differences were observed in the immunoreactivity against some gangliosides and weakly stained bands were not easy to interpret. Conclusions: Our data suggest an urgent need for standardization of commercial anti-ganglioside assays and the introduction of international anti-ganglioside antibody reference standards.