Evidence map›Paper›PMID 27113605›Full record

Trial reportJournal of neurology, neurosurgery, and psychiatry2016

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

Patrick Waters, Markus Reindl, Albert Saiz, Kathrin Schanda, Friederike Tuller, Vlastimil Kral, Petra Nytrova, Ondrej Sobek, Helle Hvilsted Nielsen, Torben Barington and 35 more

Open access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Journal of neurology, neurosurgery, and psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
163citing papers in PubMed, 2 pooled it
20.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

163 citing papers in PubMed, 2 syntheses or guidelines pooled it, 289 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2019
    Trial
  5. Article
  6. Use of Fluid Biomarkers in NMOSD and MOGAD: Clinical and Research Applications.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. [Characterization of Immune Reconstitution Patterns in B-cell Subsets Mediated by B-cell Targeted Therapies].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Observational
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  20. Article

103 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors at 20 institutions in 12 countries.

Patrick WatersNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Markus ReindlClinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Albert SaizNeuroimmunology Program, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Kathrin SchandaClinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Friederike TullerClinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Vlastimil KralZdravotni ustav se sidlem v Usti nad Labem, Centrum imunologie a mikrobiologie, Usti nad Labem, Czech Republic.
Petra NytrovaDepartment 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.
Ondrej SobekLaboratory for CSF and Neuroimmunology, Topelex Ltd, Prague, Czech Republic.
Helle Hvilsted NielsenDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Torben BaringtonDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Søren T LillevangDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Zsolt IllesInstitute of Clinical Research, University of Southern Denmark, Odense, Denmark Department of Neurology, University of Pécs, Pécs, Hungary.
Kristin RentzschEuroimmun AG, Lübeck, Germany.
Achim BertheleKlinikum rechts der Isar der TU München, Klinik für Neurologie, Munich, Germany.
Tímea BerkiDepartment of Immunology and Biotechnology, University of Pécs, Pécs, Hungary.
Letizia GranieriClinical Neurobiology Unit, Neuroscience Institute Cavalieri Ottolenghi (NICO), University Hospital San Luigi Gonzaga, Regional Referring Multiple Sclerosis Centre, Orbassano, Italy.
Antonio BertolottoClinical Neurobiology Unit, Neuroscience Institute Cavalieri Ottolenghi (NICO), University Hospital San Luigi Gonzaga, Regional Referring Multiple Sclerosis Centre, Orbassano, Italy.
Bruno GiomettoDepartment of Neurology, Azienda ULSS 9 Treviso, Treviso, Italy.
Luigi ZulianiDepartment of Neurology, Azienda ULSS 9 Treviso, Treviso, Italy.
Dörte HamannSanquin Diagnostic Services, Department of Immunopathology and Blood Coagulation, Amsterdam, The Netherlands.
E Daniëlle van PeltDepartment of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, The Netherlands.
Rogier HintzenDepartment of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, The Netherlands.
Romana HöftbergerNeuroimmunology 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.
Carme CostaServei 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.
Manuel ComabellaServei 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.
Xavier MontalbanServei 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.
Mar TintoréServei 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.
Aksel SivaNeurology Department, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey.
Ayse AltintasNeurology Department, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey.
Günnur DenizDepartment of Immunology, Istanbul University, Institute of Experimental Medicine, Istanbul, Turkey.
Mark WoodhallNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Jacqueline PalaceNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Friedemann PaulNeuroCure Clinical Research Center (NCRC), Charité Universitätsmedizin Berlin, Berlin, Germany.
Hans-Peter HartungMedical Faculty, Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Orhan AktasMedical Faculty, Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Sven JariusMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Germany.
Brigitte WildemannMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Germany.
Christian VedelerDepartment of Clinical Medicine, University of Bergen, Bergen, Norway Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Anne RuizFaculty of Medecine RTH Laennec, Lyon Neurosciences Research Centre, Neuro-inflammation and Neuro-oncology Team, Lyon, France.
M Isabel LeiteNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Peter TrillenbergDepartment of Neurology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Monika ProbstInstitute for Quality Assurance, Lübeck, Germany.
Sandra SaschenbreckerEuroimmun AG, Lübeck, Germany.
Angela VincentNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Romain MarignierFaculty of Medecine RTH Laennec, Lyon Neurosciences Research Centre, Neuro-inflammation and Neuro-oncology Team, Lyon, France.
University of Oxford · GBIstanbul University · TROdense University Hospital · DKUniversitat Autònoma de Barcelona · ESAULSS 2 Marca Trevigiana · ITCentre de Recherche en Neurosciences de Lyon · FRErasmus MC · NLEuroimmun Medizinische Labordiagnostika (Germany) · DEHeidelberg University · DEHeinrich Heine University Düsseldorf · DENeuroscience Institute · ITUniversität Innsbruck · ATUniversity of Pecs · HUCharité - Universitätsmedizin Berlin · DECharles University · CZConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESInnsbruck Medical University · ATInstitute for Research Information and Quality Assurance · DEJohn Radcliffe Hospital · GBMünchen Klinik · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveAntibodies 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).

methodsCoded 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).

resultsResults 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.

conclusionsThe 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.

Indexed as

Aquaporin 4AutoantibodiesEnzyme-Linked Immunosorbent AssayHumansImmunohistochemistryNeuromyelitis OpticaSensitivity and SpecificityAquaporin 4Autoantibodies

Identifiers

PMID27113605
PMCPMC5013123
OpenAlexW2343427124

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.