Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays
Open accessAbstract
OBJECTIVES: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). METHODS: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). RESULTS: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%-53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination. CONCLUSIONS: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis of NMO spectrum disorders and prompt initiation of disease-appropriate therapies.
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Approximately 70% of patients with relapsing NMOSD are AQP4-IgG positive, with the sensitivity increased with the use of cell-based rather than ELISA assays.
“Approximately 70% of patients with relapsing NMOSD are AQP4-IgG positive, with the sensitivity increased with the use of cell-based rather than ELISA assays.53,54”
From Diagnosis of multiple sclerosis: progress and challenges (2017) · cites this paper as [53]
The Abstract reports AQP4-IgG detection in roughly 70% of the combined NMO/NMOSD cohort and higher sensitivity for cell-based assays than for ELISA. The Methods describe some patients with recurrent disease, but the reported percentages are for the combined cohort, not specifically patients with relapsing NMOSD. (LLM, conf=0.87)
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- Authors
- Waters, P. J., McKeon, A., Leite, M. I., Rajasekharan, S., Lennon, V. A., Villalobos, A., Palace, J., Mandrekar, J. N., Vincent, A., Bar-Or, A., & Pittock, S. J.
- Affiliations
- Mayo Clinic (US)
- From the Neuroimmunology Group (P.J.W., M.I.L., J.P., A. Vincent), Nuffield Department of Clinical Neurosciences, Oxford, UK.; Departments of Neurology (A.M., V.A.L., S.J.P.), Laboratory Medicine and Pathology (A.M., V.A.L., S.J.P.), Immunology (V.A.L.), and Biostatistics (J.N.M.), Mayo Clinic, College of Medicine, Rochester, MN; Experimental Therapeutics Program (S.R., A. Villalobos, A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Canada; and Neuroimmunology Unit, Department...
- ORCID
- Venue
- Neurology
- Published
- 2012-02-28
- Volume
- 78
- Issue
- 9
- Pages
- 665-671
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3286228
- OpenAlex
- W2155112931
- Cited by
- 526
- References
- 0
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 33 · 2023: 31 · 2022: 35 · 2021: 39 · 2020: 30 · 2019: 45 · 2018: 23 · 2017: 35 · 2016: 45 · 2015: 40 · 2014: 57 · 2013: 46 · 2012: 24
- FWCI
- 38.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Biogen
- Teva Pharmaceutical Industries
- Guthy-Jackson Charitable Foundation
- Kowa Company
- National Institute for Health and Care Research
- Eisai
- Ministry of Education, Science and Technology
- Astellas Pharma
- Astellas Foundation for Research on Metabolic Disorders
- Teijin Pharma
- Mitsubishi Tanabe Pharma Corporation
- National Institutes of Health
- Japan Society for the Promotion of Science
- NIHR Oxford Biomedical Research Centre
- National Institute of Neurological Disorders and Stroke (R01NS065829, NS065829-01)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- neuromyelitis optica, aquaporin-4 antibodies, serological diagnosis, autoantibody detection, assay sensitivity and specificity, ELISA, NMO spectrum disorders, demyelinating disease, multiple sclerosis
- MeSH terms
- Adult, Humans, Immunoglobulin G, Immunoassay, Neuromyelitis Optica, Sensitivity and Specificity, Aquaporin 4
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