GD3 antibody subtyping reveals central-peripheral dichotomy in autoimmune neurological disorders

Anti-ganglioside GD3 antibodies have been implicated in the pathogenesis of autoimmune neurological disorders, yet the distinct clinical implications of their immunoglobulin subtypes remain poorly characterized. This study systematically investigates the differential clinical significance of GD3-specific IgG and IgM antibodies, as well as their co-occurrence patterns, in two neuroimmunological conditions: neuromyelitis optica spectrum disorder (NMOSD) and Guillain-Barré syndrome (GBS). Clinical data from 20 GD3 antibody-positive patients (January 2022 to January 2023) across two Chinese hospitals were retrospectively reviewed. Immunoblotting was employed to determine immunoglobulin subtypes, with subsequent analyses investigating their associations with clinical characteristics and disease outcomes. While GD3 IgG positivity demonstrated a non-significant trend with prolonged disease duration (p = 0.209), IgM seropositivity showed elevated numbness prevalence (63.6 % [7/11] vs. 22.2 % [2/9], p = 0.064). GD3/GM-GT co-positivity was associated with peripheral nerve injury (77.8 % vs 36.4 %, p = 0.092) and areflexia (55.56 % vs 9.09 %, p = 0.02). GD3/GD-dominant profiles correlated with CNS involvement (63.64 % vs 33.33 %, p = 0.18). Notably, GD3/GD dominance demonstrated significantly higher NMOSD prevalence compared to GD3/GM-GT co-positivity (45.5 % [5/11] vs. 11.1 % [1/9], p = 0.16). Our preliminary findings suggest that GD3 immunoglobulin subtypes and their co-occurrence profiles may serve as biomarkers to help distinguish between central and peripheral neurological involvement, warranting further validation in larger studies.