A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis
Abstract
Background Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. Methods Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. Findings NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was…
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Recent data suggest that some AQP4-seronegative patients with NMOSD features have antibodies reactive with MOG.
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- Authors
- Lennon, V. A., Wingerchuk, D. M., Kryzer, T. J., Pittock, S. J., Lucchinetti, C. F., Fujihara, K., Nakashima, I., & Weinshenker, B. G.
- Affiliations
- Mayo Clinic (US)
- Tohoku University (JP)
- Corresponding author
- Lennon, Vanda A
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 364
- Issue
- 9451
- Pages
- 2106-2112
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2120238028
- Cited by
- 3,239
- References
- 0
- Citations by year
- 2026: 97 · 2025: 123 · 2024: 153 · 2023: 151 · 2022: 175 · 2021: 178 · 2020: 188 · 2019: 166 · 2018: 143 · 2017: 167 · 2016: 157 · 2015: 182 · 2014: 173 · 2013: 193 · 2012: 196
- FWCI
- 50.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour and Welfare
- Community Foundation of Louisville
- Mayo Foundation for Medical Education and Research
- National Multiple Sclerosis Society (RG3185-A-2)
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- neuromyelitis optica, multiple sclerosis, aquaporin-4 antibodies, serum autoantibodies, diagnostic biomarkers, demyelinating disease, laminin, blood-brain barrier, misdiagnosis, indirect immunofluorescence
- MeSH terms
- Adult, Autoantibodies, Brain, Diagnosis, Differential, Female, Humans, Immunoglobulin G, Male, Middle Aged, Multiple Sclerosis, Neuromyelitis Optica, Optic Neuritis, Recurrence, Sensitivity and Specificity, Biomarkers, Fluorescent Antibody Technique, Indirect
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