Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum

Eoin P Flanagan; Philippe Cabre; Brian G Weinshenker; Jennifer St Sauver; Debra J Jacobson; Masoud Majed; Vanda A Lennon; Claudia F Lucchinetti; Andrew McKeon; Marcelo Matiello; Nilifur Kale; Dean M Wingerchuk; Jay Mandrekar; Jessica A Sagen; James P Fryer; Angala Borders Robinson; Sean J Pittock

doi:10.1002/ana.24617

Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum

Ann Neurol. 2016 May;79(5):775-783. doi: 10.1002/ana.24617. Epub 2016 Apr 4.

Authors

Eoin P Flanagan¹, Philippe Cabre², Brian G Weinshenker¹, Jennifer St Sauver³, Debra J Jacobson⁴, Masoud Majed¹, Vanda A Lennon^{1

5

6}, Claudia F Lucchinetti¹, Andrew McKeon^{1

5}, Marcelo Matiello⁷, Nilifur Kale⁸, Dean M Wingerchuk⁹, Jay Mandrekar⁴, Jessica A Sagen¹⁰, James P Fryer^{4

5}, Angala Borders Robinson¹¹, Sean J Pittock^{1

5}

Affiliations

¹ Department of Neurology, Mayo Clinic, Rochester, MN.
² Department of Neurology, Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Fort-de-France, Martinique, France.
³ Department of Epidemiology, Mayo Clinic, Rochester, MN.
⁴ Department of Biostatistics, Mayo Clinic, Rochester, MN.
⁵ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
⁶ Department of Immunology, Mayo Clinic, Rochester, MN.
⁷ Department of Neurology, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, MA.
⁸ Bakirkoy Prof Mazhar Osman Training and Research Hospital, Istanbul, Turkey.
⁹ Department of Neurology, Mayo Clinic, Scottsdale, AZ.
¹⁰ Neurology Research, Mayo Clinic, Rochester, MN.
¹¹ Olmsted Medical Center, Rochester, MN.

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.

Abstract

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