Serum Aquaporin 4-Immunoglobulin G Titer and Neuromyelitis Optica Spectrum Disorder Activity and Severity: A Systematic Review and Meta-Analysis.

Aquaporin 4-immunoglobulin G (AQP4-IgG) plays a major role in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Seropositive status for this antibody has become one of the required indicators for NMOSD diagnosis. Our goal was to systematically review and perform a meta-analysis of the current works of literature evaluating the clinical relevance of serum AQP4-IgG titer in patients with NMOSD. We sought to determine whether AQP4-IgG could indicate disease activity or severity, in addition to its diagnostic value in NMOSD. Electronic databases were searched for published literature, yielding 4,402 hits. Of the 124 full articles screened, 17 were included in the qualitative analysis and 14 in the meta-analysis. There were no significant differences in serum AQP4-IgG titers between the relapse and remission phases in patients with NMOSD [standard mean difference (SMD): 0.32, 95% CI (-0.10, 0.74), = 0.14]. Subgroup meta-analysis of AQP4-IgG detected by cell-based assays (CBA), an AQP4-IgG testing method recommended by the 2015 international consensus diagnostic criteria for NMOSD, confirmed the aforementioned result [SMD: 0.27, 95% CI (-0.01, 0.55), = 0.06]. Moreover, the serum AQP4-IgG titer was positively correlated with the number of involved spinal cord segments [correlation coefficient (COR): 0.70, 95% CI (0.28-0.89), = 0.003] and the Expanded Disability Status Scale (EDSS) score [COR: 0.54, 95% CI (0.06-0.82), = 0.03] in the attack phase in patients with NMOSD. The present study systematically assessed the association between serum AQP4-IgG titer and NMOSD activity and severity. The results demonstrated that the serum AQP4-IgG titer was not associated with disease activity but indicated the disease severity in the attack phase in patients with NMOSD. A further meta-analysis with a larger number of studies that employed standardized AQP4-IgG assays and detected attack-remission paired samples from the same patients with detailed medication information will be required to confirm our findings and shed more light on optimizing clinical AQP4-IgG monitoring. [www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=208209], PROSPERO, identifier [CRD42020208209].