ArticleAnnals of clinical and translational neurology2026
The Comprehensive Live Cell-Based Cytotoxicity Assay for Monitoring Disease Activity and Guiding Rescue Therapy in Acute Attacks of NMOSD.
Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveNeuromyelitis optica spectrum disorder (NMOSD) is a devastating neurological disease that lacks serological biomarkers that can accurately reflect disease activity. We established a live cell-based assay (LCBA) using serum with endogenous complement to quantify the overall cytotoxicity, offering a novel functional tool for monitoring disease activity.
methods111 samples from 65 AQP4-IgG+ NMOSD patients were enrolled in this prospective study for serological analysis of C1q, C5a, sC5b-9, CH50, and AQP4-IgG titers. A novel live cell-based complement-dependent cytotoxicity (NMO-LCBA-CDC) assay was developed using AQP4-transfected HEK293T cells exposed to test sera. Serum cytotoxicity was assessed by immunofluorescence and flow cytometry and quantified by calculating the cytotoxic index (CI). We also evaluated the cytotoxicity following intravenous methylprednisolone (IVMP) and subsequent rescue therapies.
resultsSerum C5a and sC5b-9 levels were significantly elevated during NMOSD acute attacks (p < 0.05). Following IVMP, the complement system including C5a, sC5b-9, CH50, and C1q decreased (p < 0.05), without change in AQP4-IgG titers. The CI was higher in the acute phase than in the remission phase (p = 0.0011). However, IVMP did not significantly reduce the CI during acute attacks. The NMO-LCBA-CDC assay demonstrated robust reproducibility in detecting serum cytotoxicity. Among IVMP non-responders receiving rescue therapy, both PE/IA and C5 inhibitors appeared to be associated with favorable CI reduction profiles.
conclusionBy integrating AQP4-IgG and endogenous complement activity, the NMO-LCBA-CDC assay provides a comprehensive assessment of serum cytotoxicity in NMOSD. It holds significant potential for monitoring disease activity and evaluating therapeutic effects in NMOSD.
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