Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum

Abstract

Objective: Neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDDs) with a specific biomarker, aquaporin-4-immunoglobulin G (AQP4-IgG). Prior NMO/NMOSD epidemiological studies have been limited by lack of AQP4-IgG seroprevalence assessment, absence of population-based USA studies, and under-representation of blacks. To overcome these limitations, we sought to compare NMO/NMOSD seroepidemiology across 2 ethnically divergent populations.

Methods: We performed a population-based comparative study of the incidence (2003-2011) and prevalence (on December 31, 2011) of NMO/NMOSD and AQP4-IgG seroincidence and seroprevalence (sera collected in 80-84% of IDD cases) among patients with IDD diagnosis in Olmsted County, Minnesota (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean]). AQP4-IgG was measured by M1 isoform fluorescence-activated cell-sorting assays.

Results: The age- and sex-adjusted incidence (7.3 vs 0.7/1,000,000 person-years [p < 0.01]) and prevalence (10 vs 3.9/100,000 [p = 0.01]) in Martinique exceeded that in Olmsted County. The AQP4-IgG age- and sex-adjusted seroincidence (6.5 vs 0.7/1,000,000 person-years [p < 0.01]) and seroprevalence (7.9 vs 3.3/100,000 [p = 0.04]) were also higher in Martinique than Olmsted County. The ethnicity-specific prevalence was similar in Martinique and Olmsted County: 11.5 and 13/100,000 in blacks, and 6.1 and 4.0/100,000 in whites, respectively. NMO/NMOSD represented a higher proportion of IDD cases in Martinique than Olmsted County (16% vs 1.4%; p < 0.01). The onset age (median = 35-37 years) and female:male distribution (5-9:1) were similar across both populations; 60% of prevalent cases were either blind in 1 eye, dependent on a gait aid, or both.

Interpretation: This study reports the highest prevalence of NMO/NMOSD in any population (10/100,000 in Martinique), estimates it affects 16,000 to 17,000 in the USA (higher than previous predictions), and demonstrates it disproportionately affects blacks. Ann Neurol 2016;79:775-783.

Figure 1

Flowchart of seroincidence and seroprevalence of NMOSD † MS, NMOSD, ON, TM, CIS, ADEM or other inflammatory demyelinating disorders *Olmsted County: Encephalomyelitis with meningeal involvement, 2; combined autoimmune retinopathy and optic neuropathy, 1; inflammatory leukoencephalopathy not otherwise specified, 1; and tumefactive demyelination, 1. *Martinique: suspected NMOSD but AQP4-IgG seronegative, 2; Baló’s concentric sclerosis, 2; tumefactive demyelination, 1; ‡other clinically isolated syndrome (CIS) refers to patients with single episodes of cerebral, cerebellar or brainstem demyelinating attacks alone or a single demyelinating episode with multifocal CNS involvement not meeting criteria for the other diagnoses listed. Abbreviations: ADEM, acute disseminated encephalomyelitis; AQP4-IgG, aquaporin-4-IgG; CIS, clinically isolated syndrome; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders, including NMO; ON, optic neuritis; TM, transverse myelitis.