Beyond serology: clinical and prognostic determinants in patients with dual AQP4-IgG and MOG-IgG seropositivity

Dual seropositivity for AQP4-IgG and MOG-IgG represents a rare and diagnostically challenging immunological phenotype within CNS inflammatory demyelinating disorders, and its clinical implications and prognostic significance remain poorly defined; therefore, this study was undertaken to address these gaps in knowledge.

We conducted a retrospective multicenter case series using a targeted case-ascertainment approach across neuroimmunology centers in Türkiye. The inclusion criteria were as follows: (1) confirmed dual seropositivity for AQP4-IgG and MOG-IgG through validated cell-based assays, specifically indirect immunofluorescence assay or flow cytometry-based live cell assay; (2) a clinical phenotype consistent with central nervous system inflammatory demyelination; and (3) a minimum follow-up duration of six months. Clinical, radiological, cerebrospinal fluid, therapeutic, and outcome data were systematically collected and analyzed.

Eleven patients (7 female; median age: 40 years) were included. Initial presentations included optic neuritis (n = 7) and myelitis (n = 4). Longitudinally extensive transverse myelitis was observed in 4 patients (36.4%), while 3 had short-segment lesions. Long-segment optic nerve hyperintensity was seen in 5 of 7 optic neuritis cases. Two patients relapsed and two died due to systemic comorbid conditions. At last follow-up, patients with comorbidities had significantly higher EDSS scores than those without comorbidities (median: 4.0 vs. 1.0; p = 0.008).

Although dual AQP4-IgG and MOG-IgG seropositivity is rare, it is clinically significant. Prognosis is more strongly influenced by systemic comorbidities and overall clinical burden than by serostatus alone. Clinical management should therefore be guided by the overall disease phenotype and coexisting systemic conditions rather than antibody status in isolation.