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J Neuroimmunol. 2019 Jan 15;326:19-27. doi: 10.1016/j.jneuroim.2018.11.002. Epub 2018 Nov 7.

Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis. Results from the ABIRISK prospective cohort study.

Author information

1
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: poul.erik.h.jensen@regionh.dk.
2
Department of Neurology, University Hospital Köln, Köln, Germany; University of Düsseldorf, Medical Faculty, Department of Neurology, Düsseldorf, Germany. Electronic address: clemens.warnke@uk-koeln.de.
3
University of Düsseldorf, Medical Faculty, Department of Neurology, Düsseldorf, Germany. Electronic address: Kathleen.Ingenhoven@med.uni-duesseldorf.de.
4
Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland. Electronic address: luca.piccoli@irb.usi.ch.
5
University of Düsseldorf, Medical Faculty, Department of Neurology, Düsseldorf, Germany. Electronic address: gasis@hhu.de.
6
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: christina.hermanrud@ki.se.
7
Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland. Electronic address: blanca.fernandez@irb.usi.ch.
8
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
9
Sanofi-Aventis Germany, Frankfurt Am Main, Germany. Electronic address: daniel.kramer@sanofi.com.
10
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: jenny.link@ki.se.
11
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; KTH - Royal Institute of Technology, Stockholm, Sweden. Electronic address: Ryan.Ramanujam@ki.se.
12
Innsbruck Medical University, Innsbruck, Austria. Electronic address: Michael.Auer@student.i-med.ac.at.
13
Department of Neurology, Technische Universität München, Munich, Germany. Electronic address: dorothea.buck@tum.de.
14
Department of Neurology, Technische Universität München, Munich, Germany. Electronic address: v.grummel@tum.de.
15
Merck NBE Bioanalytics Ivrea, Colleretto Giacosa, Italy. Electronic address: elisa.bertotti@merckgroup.com.
16
Hospital Universitari Vall d'Hebron, Centre d'Esclerosi Múltiple de Catalunya, Barcelona, Spain. Electronic address: nicolas.fissolo@vhir.org.
17
Hospital Regional Universitario de Málaga, Instituto de investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.
18
MS Center, Department of Neurology and Center Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic. Electronic address: Petra.Nytrova@lf1.cuni.cz.
19
Department of Neurology, Medical University of Graz, Graz, Austria. Electronic address: michael.khalil@medunigraz.at.
20
Clinic for Neurology 2, Kepler University Clinic, Med Campus III, Linz, Austria. Electronic address: Michael.Guger@kepleruniklinikum.at.
21
Clinic for Neurology 2, Kepler University Clinic, Med Campus III, Linz, Austria. Electronic address: Sandra.Rathmaier@kepleruniklinikum.at.
22
Departments of Biomedicine and Neurology, University Hospital Basel and University of Basel, Basel, Switzerland. Electronic address: claudia.sievers-stober@unibas.ch.
23
Departments of Biomedicine and Neurology, University Hospital Basel and University of Basel, Basel, Switzerland. Electronic address: Raija.Lindberg@unibas.ch.
24
CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay, University UVSQ, Villejuif, France. Electronic address: signe.hassler@inserm.fr.
25
CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay, University UVSQ, Villejuif, France. Electronic address: delphine.bachelet@inserm.fr.
26
University of Düsseldorf, Medical Faculty, Department of Neurology, Düsseldorf, Germany. Electronic address: orhan.aktas@uni-duesseldorf.de.
27
Ipsen Biopharm Ltd., Berkshire, United Kingdom.
28
GlaxoSmithKline R&D, Uxbridge, Middlesex, United Kingdom. Electronic address: andy.m.lawton@gsk.com.
29
Department of Neurology, Technische Universität München, Munich, Germany; Munich Cluster for systems Neurology (SyNergy), Munich, Germany. Electronic address: hemmer@lrz.tu-muenchen.de.
30
MS Center, Department of Neurology and Center Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic. Electronic address: eva.havrdova@lf1.cuni.cz.
31
University of Düsseldorf, Medical Faculty, Department of Neurology, Düsseldorf, Germany. Electronic address: Bernd.Kieseier@uni-duesseldorf.de.
32
University of Düsseldorf, Medical Faculty, Department of Neurology, Düsseldorf, Germany. Electronic address: hans-peter.hartung@uni-duesseldorf.de.
33
Hospital Universitari Vall d'Hebron, Centre d'Esclerosi Múltiple de Catalunya, Barcelona, Spain. Electronic address: manuel.comabella@vhir.org.
34
Hospital Universitari Vall d'Hebron, Centre d'Esclerosi Múltiple de Catalunya, Barcelona, Spain. Electronic address: xavier.montalban@unic-em.com.
35
Departments of Biomedicine and Neurology, University Hospital Basel and University of Basel, Basel, Switzerland. Electronic address: Tobias.Derfuss@usb.ch.
36
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: finn.thorup.sellebjerg@regionh.dk.
37
SciCross AB, Skövde, Sweden. Electronic address: pierre@scicross.com.
38
INSERM UMR 996, Univ. Paris-Sud, Faculty of Pharmacy, Université Paris-Saclay, Châtenay-Malabry, France. Electronic address: marc.pallardy@u-psud.fr.
39
Drug Metabolism Pharmacokinetics-Biologics, Novartis Institutes for Biomedical Research, Basel, Switzerland. Electronic address: sebastian.spindeldreher@novartis.com.
40
CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay, University UVSQ, Villejuif, France; Assistance Publique - Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France. Electronic address: philippe.broet@inserm.fr.
41
Innsbruck Medical University, Innsbruck, Austria. Electronic address: Florian.Deisenhammer@tirol-kliniken.at.
42
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Anna.Fogdell-Hahn@ki.se.
43
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: Per.Soelberg.Soerensen@regionh.dk.

Abstract

Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.

KEYWORDS:

Anti-drug antibodies; Bridging ELISA; Interferon-beta; Luciferase-based bioassay; Multiple sclerosis; Neutralizing antibodies

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