Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a clinically defined, inflammatory central nervous system (CNS) disease of unknown cause, associated with humoral autoimmune findings such as anti-aquaporin 4 (AQP4)-IgG. Recent clinical trials showed benefit anti-B cell and anti-complement-antibodies in NMOSD, suggesting relevance anti-AQP4-IgG pathogenesis. Objective: AQP4-IgG NMOSD clearly yet up to 40% the patients are negative for AQP4-IgG. This may indicate that not disease-driving or defines distinct patient endotype. Methods: We established biobank 63 well-characterized an extensive annotation 351 symptoms, characteristics, laboratory results scores. used phylogenetic clustering, heatmaps, principal component longitudinal causal interference analyses test anti-AQP4-IgG. Results: Anti-AQP4-IgG was undetectable 29 (46%) patients. Within anti-AQP4-IgG-positive patients, titers did correlate activity. Comparing vs. -negative delineate any defined subgroup. However, positive had significantly ( p = 0.022) higher rate additional diagnoses. Conclusion: Our challenge assumption alone plays role NMOSD. might represent epiphenomenon one several immune mechanisms collectively contribute pathogenesis this indeed, be relevant factor only subgroup