Influencing factors and clinical value of anti-aquaporin-4 antibody in cerebrospinal fluid: a study of 82 patients with neuromyelitis optica spectrum disorder.

Objective: Serum AQP4 antibody (AQP4-IgG) is the causative antibody of neuromyelitis optica spectrum disorder (NMOSD) but AQP4-IgG in cerebrospinal fluid (CSF) has been seldom studied. We aimed to explore the clinical value and influencing factors of CSF AQP4-IgG in NMOSD.

Methods: In this study, we screened 137 patients with NMOSD diagnosed according to the 2015 International Consensus Diagnostic Criteria (IPND criteria). From this cohort, paired CSF and serum samples were simultaneously collected from 82 patients (including seropositive and seronegative subgroups) for antibody titer measurement. We explored the relationship between CSF AQP4-IgG and patient's clinical features. Their demographic, clinical, laboratory data and MRI images were collected and analyzed.

Results: 74 patients were seropositive for AQP4-IgG and 8 patients were seronegative. Among the 74 patients seropositive for AQP4-IgG, 46 were CSF-positive and 28 were CSF-negative, while none of the 8 seronegative patients were CSF-positive. CSF AQP4-IgG positive and negative patients showed significant differences in EDSS and relapse status. Out of the 82 patients, 67 patients were during relapse and only patients during relapse were included in the next analysis. Between the CSF-positive and CSF-negative patients, no significant differences were found in EDSS, relapse manifestation, CSF indicators, serum cytokine levels, lymphocyte subsets or MRI lesions. Responses to treatment during relapse and length of hospital stay showed no significant differences either. A positive correlation between the serum and CSF titers (rs: 0.64, p < 0.001) was found. Further binary logistic regression analysis revealed that CSF AQP4-IgG positivity was associated with serum AQP4-IgG titers and EDSS scores.

Conclusions: CSF AQP4-IgG positivity primarily results from passive diffusion of serum antibodies across the blood-brain barrier, which is different from the CNS-restricted antibody production in MOG-IgG associated disorders (MOGAD). Limited prognostic value of CSF AQP4-IgG was revealed in this study.