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Abstract
Objective: To optimize aquaporin-4 (AQP4) antibody (Ab) detection and to assess the influence of the increased sensitivity of the assay on the demographic and disease-related characteristics of a group of AQP4-Ab–negative patients.
Methods: Serum samples were obtained from patients included in the French NOMADMUS database with a definite diagnosis of neuromyelitis optica (NMO) (n = 87) and were compared with controls (n = 54). They were tested by indirect immunofluorescence and cell-based assays (CBAs) in various conditions and with several plasmids.
Results: We identified the CBA on live cells transfected with the untagged AQP4-M23 isoform as the best method, with a sensitivity of 74.4% and a specificity of 100%. We demonstrated a direct relationship between improvement of the sensitivity of the detection method and the distinctiveness and characteristics of the AQP4-Ab–negative NMO group. Whereas with the classic indirect immunofluorescence or current AQP4-M1 CBA we found only slight differences between the 2 populations, using the AQP4-M23 CBA, we demonstrated that patients with AQP4-Ab–negative NMO expressed specific demographic and disease-related features. They were characterized by an equal male/female ratio (p < 0.001), a Caucasian ethnicity (p = 0.029), and an overrepresentation of simultaneous optic neuritis and transverse myelitis at first episode (p = 0.015). In terms of disability, they experienced a better visual acuity at last follow-up compared with seropositive NMO (p = 0.007).
Conclusion: This raises the question of a distinct physiopathology for patients with AQP4-Ab–negative NMO and of their place in the spectrum of the disease.
Glossary
- Ab=
- antibody;
- AQP4=
- aquaporin-4;
- CBA=
- cell-based assay;
- EGFP=
- enhanced green fluorescent protein;
- NMO=
- neuromyelitis optica;
- EDMUS=
- European Database for Multiple Sclerosis;
- Ig=
- immunoglobulin;
- MS=
- multiple sclerosis;
- NOMADMUS=
- European Database for Multiple Sclerosis Adapted to Neuromyelitis Optica Specificities
Footnotes
NOMADMUS Study Group coinvestigators are listed on the Neurology® Web site at www.neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 2176
Supplemental data at www.neurology.org
- Received October 9, 2012.
- Accepted in final form February 12, 2013.
- © 2013 American Academy of Neurology
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