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February 1, 2012

Serologic diagnosis of NMO
A multicenter comparison of aquaporin-4-IgG assays

P.J. Waters, PhD, A. McKeon, MB, MRCPI, M.I. Leite, MD, DPhil, S. Rajasekharan, PhD, V.A. Lennon, MD, PhD, A. Villalobos, MSc, J. Palace, DM, FRCP, J.N. Mandrekar, PhD, A. Vincent, MBBS, FRCPath, A. Bar-Or, MD, FRCP(C), and S.J. Pittock, MDAuthors Info & Affiliations
February 28, 2012 issue
78 (9) 665-671
https://doi.org/10.1212/WNL.0b013e318248dec1
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Abstract

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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Supplementary Material

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REFERENCES

1.
Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805–815.
Crossref
PubMed
Google Scholar
2.
Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485–1489.
Crossref
PubMed
Google Scholar
3.
Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106–2112.
Crossref
PubMed
Google Scholar
4.
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005;202:473–477.
Crossref
PubMed
Google Scholar
5.
Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 2007;69:2221–2231.
Crossref
PubMed
Google Scholar
6.
Hinson SR, Roemer SF, Lucchinetti CF, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med 2008;205:2473–2481.
Crossref
PubMed
Google Scholar
7.
Bradl M, Misu T, Takahashi T, et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol 2009;66:630–643.
Crossref
PubMed
Google Scholar
8.
Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of NMO-IgG and human complement produces neuromyelitis optica lesions in mice. Brain 2010;133:349–361.
Crossref
PubMed
Google Scholar
9.
Kinoshita M, Nakatsuji Y, Kimura T, et al. Neuromyelitis optica: passive transfer to rats by human immunoglobulin. Biochem Biophys Res Commun 2009;386:623–627.
Crossref
PubMed
Google Scholar
10.
Bennett JL, Lam C, Kalluri SR, et al. Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol 2009;66:617–629.
Crossref
PubMed
Google Scholar
11.
Waters P, Jarius S, Littleton E, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 2008;65:913–919.
Crossref
PubMed
Google Scholar
12.
Jarius S, Franciotta D, Bergamaschi R, et al. NMO-IgG in the diagnosis of neuromyelitis optica. Neurology 2007;68:1076–1077.
Crossref
PubMed
Google Scholar
13.
McKeon A, Fryer J, Apiwattanakul M, et al. Diagnosis of neuromyelitis spectrum disorders: comparative sensitivities and specificities of immunohistochemical and immunoprecipitation assays. Arch Neurol 2009;66:1134–1138.
Crossref
PubMed
Google Scholar
14.
Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007;130:1235–1243.
Crossref
PubMed
Google Scholar
15.
Jarius S, Probst C, Borowski K, et al. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 2010;291:52–56.
Crossref
PubMed
Google Scholar
16.
Hayakawa S, Mori M, Okuta A, et al. Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay. J Neuroimmunol 2008;196:181–187.
Crossref
PubMed
Google Scholar
17.
De Vidi I, Boursier G, Delouche N, et al. Strategy for anti-aquaporin-4 auto-antibody identification and quantification using a new cell-based assay. Clin Immunol 2011;138:239–246.
Crossref
PubMed
Google Scholar
18.
Takahashi T, Fujihara K, Nakashima I, et al. Establishment of a new sensitive assay for anti-human aquaporin-4 antibody in neuromyelitis optica. Tohoku J Exp Med 2006;210:307–13.
Crossref
PubMed
Google Scholar
19.
Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol 2009 Sep;66:1164–1167.
Crossref
PubMed
Google Scholar

Information & Authors

Information

Published In

Neurology®
Volume 78 • Number 9 • February 28, 2012
Pages: 665-671
PubMed: 22302543

Copyright

Copyright © 2012 by AAN Enterprises, Inc.

Publication History

Received: May 19, 2011
Accepted: August 12, 2011
Published online: February 1, 2012
Published in print: February 28, 2012

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Disclosure

Dr. Waters is a named inventor on a patent relating to assays for the detection of antibodies to Lgi1, Caspr2, and Contactin2 and may receive royalties for this technology. Dr. Waters receives research support from the Oxford NIHR Biomedical Research Centre. Dr. McKeon receives research support from the Guthy Jackson Charitable Foundation. Dr. Leite receives research support from the Oxford Biomedical Research Centre, the National Commissioning Group, and the Sir Halley Stewart Trust, UK. Dr. Rajasekharan reports no disclosures. Dr. Lennon is a named inventor on a patent relating to aquaporin-4 antibodies for diagnosis of neuromyelitis optica and receives royalties for this technology; is a named inventor on patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; and receives research support from the Guthy Jackson Charitable Foundation. A. Villalobos reports no disclosures. Dr. Palace serves on scientific advisory boards for Merck Serono, Bayer Schering Pharma, Biogen Idec, Teva Pharmaceutical Industries Ltd., Novartis, and sanofi-aventis; has received funding for travel from Merck Serono; and receives research support from the Multiple Sclerosis Society and the Department of Health Risk Sharing Scheme (Clinical Coordinator). Dr. Mandrekar reports no disclosures. Dr. Vincent is a named inventor on a patent relating to assays for the detection of antibodies to Lgi1, Caspr2, and Contactin2 and may receive royalties for this technology. Dr. Vincent has served on scientific advisory boards for the Patrick Berthoud Trust and the Myasthenia Gravis Foundation of America; has received funding for travel and a speaker honorarium from Baxter International Inc.; serves as an Associate Editor for Brain; receives royalties from the publication of Clinical Neuroimmunology (Blackwell Publishing, 2005) and Inflammatory and Autoimmune Disorders of the Nervous System in Children (Mac Keith Press, 2010); receives research support from the European Union, the Oxford NIHR Biomedical Research Centre, and Sir Halley Stewart Trust; and has received Musk antibody royalties and consulting fees from Athena Diagnostics, Inc. and Musk antibody royalties from RSR Ltd., Cardiff, UK. The University of Oxford, where A.V. is based, receives royalties and payments for antibody assays in neurologic diseases. Dr. Bar-Or serves on scientific advisory boards for BioMS Medical, DioGenix, Inc., Ono Pharmaceutical Co. Ltd., GlaxoSmithKline, Roche, Guthy Jackson Greater Good Foundation, and NMO Research and Clinical Care Consortium; serves on the editorial boards of Neurology® and Clinical and Experimental Neuroimmunology; has received speaker honoraria from Biogen Idec, Bayhill Therapeutics, Bayer Schering Pharma (Berlex), Eli Lilly and Company, Genentech, Inc., GlaxoSmithKline, Merck Serono, Novartis, Wyeth, sanofi-aventis, and Teva Pharmaceutical Industries Ltd.; and receives/has received research support from BioMS Medical, Merck Serono, Bayhill Therapeutics, Biogen Idec, Genentech, Inc., and Teva Pharmaceutical Industries Ltd. Dr. Pittock is a named inventor on patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; receives research support from Alexion Pharmaceuticals, Inc., the Guthy Jackson Charitable Foundation, and the NIH.

Authors

Affiliations & Disclosures

P.J. Waters, PhD*
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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A. McKeon, MB, MRCPI
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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M.I. Leite, MD, DPhil
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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S. Rajasekharan, PhD
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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V.A. Lennon, MD, PhD
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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A. Villalobos, MSc
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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J. Palace, DM, FRCP
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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J.N. Mandrekar, PhD
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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A. Vincent, MBBS, FRCPath
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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A. Bar-Or, MD, FRCP(C)
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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S.J. Pittock, MD*
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 of Neurology and Neurosurgery (A.B-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
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Notes

*
These authors contributed equally to this work.
Study funding: Supported in part by The Guthy-Jackson Charitable Foundation and NIH (NS065829-01). P.J.W., M.I.L., J.P., and A.Vincent are supported by the NIHR and the NIHR Oxford Biomedical Research Centre.
Correspondence & reprint requests to Dr. Pittock: [email protected] or Dr. Waters: [email protected]

Author Contributions

Study design and conceptualization: P.J.W., A.B.-O., S.P. Drafting of manuscript: P.J.W., S.J.P. Acquisition, analysis and interpretation of data: P.J.W., A.M., M.I.L., S.R., V.A.L, A.V., J.P., J.N.M., A.Villalobos, A.B.-O., S.J.P. Statistical analysis: P.J.W., J.N.M., S.J.P. Critical revision of the manuscript: P.J.W., A.M., M.I.L., S.R., V.A.L., A.Villalobos, J.P., J.N.M., A.Vincent, A.B.-O., S.J.P.

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