The occurrence of myelin oligodendrocyte glycoprotein antibodies in aquaporin-4-antibody seronegative Neuromyelitis Optica Spectrum Disorder: A systematic review and meta-analysis

Background: Despite inclusion in neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases are increasingly recognized as an independent disease entity. In this study, we conducted a systematic review and meta-analysis to comprehensively update the rate of occurrence of MOG-Ab in Aquaporin4 (AQP4)-antibody seronegative NMOSD. Methods: We searched PubMed, EMBASE, and Cochrane databases for studies reporting the rates of patients with MOG-Ab in NMOSD. Fixed or random-effects models were used to pool results across studies. Results: Fourteen studies met the inclusion criteria. Overall, MOG-Abs positive patients comprised 9.3% of all NMO/NMOSD (95% confidence interval [CI] 7.9%-10.8%, I-2 = 13.1%), 32.5% of all AQP4-Ab seronegative NMO/NMOSD (95% CI 25.7%-39.3%, I-2 = 45.8%), and 41.6% of AQP4-Ab seronegative NMOSD cases diagnosed by IPND 2015 criteria (95% CI 35.1%-48.2%, I-2 = 0.0%). The pooled prevalence of MOG-Ab was 31.0% among Asian AQP4-Ab seronegative NMO/NMOSD patients (95% CI 22.1%-39.9% I-2=54.1%) and 34.3% in European seronegative NMO/NMOSD (95% CI 21.9%-46.7%, I-2 = 51.9%). Conclusions: This study shows that MOG-Abs represent a substantial proportion of AQP4-Ab seronegative NMOSD patients despite different underlying mechanisms, clinical manifestations, and treatment response, suggesting MOG-Ab screening in AQP4-Ab seronegative NMOSD patients can facilitate accurate diagnoses and treatments.