Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica
- PMID: 23997151
- PMCID: PMC3795610
- DOI: 10.1212/WNL.0b013e3182a6cb5c
Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica
Abstract
Objective: To 1) determine, using contemporary recombinant antigen-based assays, the aquaporin-4 (AQP4)-immunoglobulin G (IgG) detection rate in sequential sera of patients assigned a clinical diagnosis of neuromyelitis optica (NMO) but initially scored negative by tissue-based indirect immunofluorescence (IIF) assay; and 2) evaluate the impact of serostatus on phenotype and outcome.
Methods: From Mayo Clinic records (2005-2011), we identified 163 patients with NMO; 110 (67%) were seropositive by IIF and 53 (33%) were scored seronegative. Available stored sera from 49 "seronegative" patients were tested by ELISA, AQP4-transfected cell-based assay, and in-house fluorescence-activated cell sorting assay. Clinical characteristics were compared based on final serostatus.
Results: Thirty of the 49 IIF-negative patients (61%) were reclassified as seropositive, yielding an overall AQP4-IgG seropositivity rate of 88% (i.e., 12% seronegative). The fluorescence-activated cell sorting assay improved the detection rate to 87%, cell-based assay to 84%, and ELISA to 79%. The sex ratio (female to male) was 1:1 for seronegatives and 9:1 for seropositives (p < 0.0001). Simultaneous optic neuritis and transverse myelitis as onset attack type (i.e., within 30 days of each other) occurred in 32% of seronegatives and in 3.6% of seropositives (p < 0.0001). Relapse rate, disability outcome, and other clinical characteristics did not differ significantly.
Conclusions: Serological tests using recombinant AQP4 antigen are significantly more sensitive than tissue-based IIF for detecting AQP4-IgG. Testing should precede immunotherapy; if negative, later-drawn specimens should be tested. AQP4-IgG-seronegative NMO is less frequent than previously reported and is clinically similar to AQP4-IgG-seropositive NMO.
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Comment in
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AQP4 antibody serostatus: Is its luster being lost in the management and pathogenesis of NMO?Neurology. 2013 Oct 1;81(14):1186-8. doi: 10.1212/WNL.0b013e3182a6cc23. Epub 2013 Aug 30. Neurology. 2013. PMID: 23997154 No abstract available.
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Neuroimmunology: Aquaporin-4-antibody-seronegative neuromyelitis optica is less common than previously thought.Nat Rev Neurol. 2013 Nov;9(11):604. doi: 10.1038/nrneurol.2013.196. Epub 2013 Sep 17. Nat Rev Neurol. 2013. PMID: 24042481 No abstract available.
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