Analysis of MOG-IgG and AQP4-IgG Serology, Demographics, and Seasonality From Large Neuroimmunology Laboratory Registry and Clinical Cohorts

Background: Large-scale studies examining the demographic, serological, and seasonal characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) remain limited, despite their potential to provide crucial information for resource allocation, clinical trial design, and recruitment. Objective: To investigate demographic, serological, and seasonal variations in MOGAD and AQP4+NMOSD using a large neuroimmunology laboratory registry validated by clinical cohorts. Methods: We conducted a retrospective, laboratory-based study using data from the Mayo Clinic Neuroimmunology Laboratory registry and clinical cohorts between July 2014 and April 2024. The first available serum sample from each patient tested for MOG-IgG and AQP4-IgG was included. Analyses focused on age and sex distributions, antibody titers, and seasonal patterns of seropositivity, as well as the month and season of disease onset and attacks among the clinical cohorts of MOGAD and AQP4+NMOSD. Results: We included 89,495 sera tested for MOG-IgG and 198,401 for AQP4-IgG, supplemented by validated clinical cohorts of 528 patients with MOGAD and 534 with AQP4+NMOSD. MOG-IgG was detected in 6,313 samples (7.1%), with 1,566 (24.8%) exhibiting high titers (≥1:1,000). AQP4-IgG was positive in 5,057 samples (2.5%). Individuals with MOG-IgG positivity were younger than those with AQP4-IgG positivity (mean age, 34.1 years [SD=20.0] vs 47.7 years [SD=17.9]; p<0.0001). The frequency of MOG-IgG positivity was highest among patients younger than 12 years (1,052 [17.9%]) and declined with older age, while AQP4-IgG positivity increased with older age. AQP4-IgG revealed a strong female predilection (female-to-male ratio 6.2:1), varying by age, whereas MOG-IgG showed a modest female predominance (female-to-male ratio 1.5:1), consistent across all ages. MOG-IgG-titers peaked in younger children and older adults, while AQP4-IgG titers remained stable across ages. Both diseases showed a winter peak in seropositivity, disease onset, and relapses. Conclusions: This large-scale registry analysis provides comprehensive demographic and serological characterization of MOGAD and AQP4+NMOSD. The modest winter peak suggests that seasonal infectious triggers may play an important role in disease pathogenesis. Limitations include incomplete clinical information within the laboratory registry and a referral-based testing population. These findings have important implications for healthcare planning and optimization of clinical trial design and recruitment.