Abstract
BACKGROUND: This study aimed to compare clinical outcomes in NMOSD patients with non-AQP4-IgG autoantibodies, specifically anti-connective tissue disease antibodies (anti-CTD Abs) and antithyroid antibodies (ATAbs), to evaluate their impact on disease severity and prognosis. METHODS: A retrospective analysis was conducted using data from NMOSD inpatients with follow-up periods ≥180 days, stratified by antibody status: anti-CTD Abs (+)/(-), ATAbs (+)/(-), or double positivity (+)/(-). The primary outcomes included relapse rates, Expanded Disability Status Scale (EDSS) scores, and survival outcomes. RESULTS: (1) Anti-CTD Abs (+): higher proportion of female patients, increased relapse frequency; decreased red blood cell (RBC) count and aspartate aminotransferase (AST) levels. (2) ATAbs (+): greater incidence of acute brainstem syndrome (ABS); reduced peripheral leukocyte, neutrophil, and lymphocyte counts; elevated serum urea levels. (3) Double (+): marked female predominance, higher incidence of ABS, decreased RBC count, hemoglobin (Hb) levels, and cerebrospinal fluid (CSF) chloride concentration; elevated serum urea. (4) AQP4-IgG association: AQP4-IgG-positive patients were more frequently female, with higher prevalence of anti-CTD Abs positivity but lower prevalence of ATAbs positivity. (5) Prognostic analysis: both double-positive and single-antibody-positive groups showed higher disability (EDSS ≥4.0/≥6.0) compared with antibody-negative patients, although no significant differences were observed between the two single-antibody subgroups. (6) Multivariate analysis identified combined antibody positivity (OR = 16.292), baseline EDSS score (OR = 3.179), and age at onset (OR = 1.052) as independent predictors of poor clinical outcomes. CONCLUSION: Routine screening for anti-CTD Abs and ATAbs in NMOSD patients may aid in assessing disease severity and prognosis. Patients with double positivity represent a high-risk subgroup requiring aggressive therapeutic strategies to prevent severe disability.