Fluctuations in serum aquaporin-4 antibody titers: the clinical significance in neuromyelitis optica spectrum disorder.

Objective: To evaluate the relationship between aquaporin-4 immunoglobulin G (AQP4-IgG) titer dynamics and relapse in neuromyelitis optica spectrum disorder (NMOSD), compare AQP4-IgG dynamics across different maintenance therapy strategies, and identify factors associated with AQP4-IgG titer seroreversion to negativity.

Methods: Altogether 171 patients with ≥ 2 serum AQP4-IgG tests by fixed cell-based assay 30 days apart and at least once positive were included. Their clinical and treatment data were reviewed.

Results: Among the 171 NMOSD patients with a median disease duration of 81.3 months, 44 (25.7%) became AQP4-IgG seronegative, accompanied by a reduction in annualized relapse rate (0.16 vs. 0.00, P < 0.001). Decline in serum AQP4-IgG titers emerged as the protective factor against relapse (HR 0.53, 95% CI 0.36-0.79, P = 0.002). Patients receiving monoclonal antibodies (mostly B cell-depleting therapies) as their initial and sole therapy throughout disease demonstrated higher likelihood of AQP4-IgG seroreversion compared to those treated with non-specific immunosuppressants (HR 3.01, 95% CI 1.23-7.34, P = 0.016) or those started with immunosuppressants and later switched to monoclonal antibodies (HR 6.17, 95% CI 2.13-17.54, P < 0.001). Male (OR 3.95, 95% CI 1.35-11.63, P = 0.012), baseline AQP4-IgG titer (OR 0.71, 95% CI 0.55-0.92, P = 0.008) and monoclonal antibody treatment throughout disease (OR 4.07, 95% CI 1.45-11.40, P = 0.008) were independently associated with AQP4-IgG seroreversion.

Conclusions: Serum AQP4-IgG titer is related with relapse risk. Early initiation of monoclonal antibodies shows a superior suppressive effect on AQP4 autoimmunity.