Testing for antibodies to human aquaporin-4 by ELISA: sensitivity, specificity, and direct comparison with immunohistochemistry

Background Several assays have been developed to detect antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab). However, many of these assays require sophisticated techniques and are thus only available at specialized laboratories. This is problematic since NMO-IgG/AQP4-Ab testing has important prognostic and...

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Main Authors: Jarius, Sven (Author) , Wildemann, Brigitte (Author)
Format: Article (Journal)
Language:English
Published: 16 June 2012
In: Journal of the neurological sciences
Year: 2012, Volume: 320, Issue: 1, Pages: 32-37
ISSN:1878-5883
DOI:10.1016/j.jns.2012.06.002
Online Access:Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022510X12002857
Verlag, Volltext: http://dx.doi.org/10.1016/j.jns.2012.06.002
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Author Notes:S. Jarius, D. Franciotta, F. Paul, R. Bergamaschi, P. S. Rommer, K. Ruprecht, M. Ringelstein, O. Aktas, W. Kristoferitsch, B. Wildemann

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520 |a Background Several assays have been developed to detect antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab). However, many of these assays require sophisticated techniques and are thus only available at specialized laboratories. This is problematic since NMO-IgG/AQP4-Ab testing has important prognostic and therapeutic implications. Objective To evaluate a newly developed, commercial, enzyme-linked immunosorbent assay (ELISA) for detecting NMO-IgG/AQP4-Ab. Methods Serum samples from 261 patients with NMO spectrum disorders (NMOSD; n=108) and controls (n=153) were tested for AQP4-Ab by using ELISA. Of these patients, 207 were tested in parallel using a standard immunohistochemical (IHC) assay. Results Fifty of 66 (75.8%) patients with NMO, 17/25 (68%) with LETM, 3/14 (21.4%) with ON, 2/3 (66.7%) with ON and non-extensive transverse myelitis, and 2/153 (1.3%) controls tested positive in the ELISA. Of those NMOSD patients tested by both ELISA and IHC, 10 were positive only in the ELISA and 3 exclusively in the IHC assay, suggesting that the overall sensitivity of the ELISA was higher than that of the standard IHC assay. The ELISA yielded very good intra- and inter-run reproducibility with regard to AQP4-Ab detection and good intrarun, but only moderate inter-run reproducibility with regard to AQP4-Ab quantification. Anti-AQP4 serum concentrations correlated with disease activity (p<0.00001), but did not differ between patients with NMO and patients with isolated LETM or ON. Conclusion The ELISA evaluated here provides a relatively sensitive and easy-to-use diagnostic tool for detecting antibodies to AQP4 and could make AQP4-Ab testing, which is of high clinical relevance, more widely available. 
650 4 |a Antibody to aquaporin-4 
650 4 |a Diagnosis 
650 4 |a Enzyme-linked immunosorbent assay (ELISA) 
650 4 |a Indirect immunofluorescence 
650 4 |a Longitudinally extensive transverse myelitis 
650 4 |a Multiple sclerosis 
650 4 |a Neuromyelitis optica (Devic's syndrome) 
650 4 |a NMO-IgG 
650 4 |a Optic neuritis 
650 4 |a Recombinant antigen 
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