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Background:  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.   Objective:  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.   Methods:  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.   Results:  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),  p  = 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),  p  = 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),  p  = 0.003] and the Expanded Disability Status Scale (EDSS) score [COR: 0.54, 95% CI (0.06-0.82),  p  = 0.03] in the attack phase in patients with NMOSD.   Conclusions:  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.   Systematic Review Registration:  [ www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=208209 ], PROSPERO, identifier [CRD42020208209].

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