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J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):1005-15. doi: 10.1136/jnnp-2015-312601. Epub 2016 Apr 25.

Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica.

Author information

1
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
2
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
3
Neuroimmunology Program, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
4
Zdravotni ustav se sidlem v Usti nad Labem, Centrum imunologie a mikrobiologie, Usti nad Labem, Czech Republic.
5
Department of Neurology, Center of Clinical Neuroscience First Faculty of Medicine, General University Hospital and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
6
Laboratory for CSF and Neuroimmunology, Topelex Ltd, Prague, Czech Republic.
7
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
8
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Department of Neurology, University of Pécs, Pécs, Hungary.
9
Euroimmun AG, Lübeck, Germany.
10
Klinikum rechts der Isar der TU München, Klinik für Neurologie, Munich, Germany.
11
Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary.
12
Clinical Neurobiology Unit, Neuroscience Institute Cavalieri Ottolenghi (NICO), University Hospital San Luigi Gonzaga, Regional Referring Multiple Sclerosis Centre, Orbassano, Italy.
13
Department of Neurology, Azienda ULSS 9 Treviso, Treviso, Italy.
14
Sanquin Diagnostic Services, Department of Immunopathology and Blood Coagulation, Amsterdam, The Netherlands.
15
Department of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, The Netherlands.
16
Neuroimmunology Program, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain Institute of Neurology, Medical University of Vienna, Vienna, Austria.
17
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
18
Neurology Department, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey.
19
Department of Immunology, Istanbul University, Institute of Experimental Medicine, Istanbul, Turkey.
20
NeuroCure Clinical Research Center (NCRC), Charité Universitätsmedizin Berlin, Berlin, Germany.
21
Medical Faculty, Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
22
Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Germany.
23
Department of Clinical Medicine, University of Bergen, Bergen, Norway Department of Neurology, Haukeland University Hospital, Bergen, Norway.
24
Faculty of Medecine RTH Laennec, Lyon Neurosciences Research Centre, Neuro-inflammation and Neuro-oncology Team, Lyon, France.
25
Department of Neurology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
26
Institute for Quality Assurance, Lübeck, Germany.

Abstract

OBJECTIVE:

Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD).

METHODS:

Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1).

RESULTS:

Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples.

CONCLUSIONS:

The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.

PMID:
27113605
PMCID:
PMC5013123
DOI:
10.1136/jnnp-2015-312601
[Indexed for MEDLINE]
Free PMC Article

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