Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies

Hans Peter Hartung, Bernd Kieseier, Douglas S. Goodin, Barry G W Arnason, Giancarlo Comi, Stuart Cook, Massimo Filippi, Douglas R. Jeffery, Ludwig Kappos, Timon Bogumil, Brigitte Stemper, Rupert Sandbrink, Yukiko Nakada, Haruhiko Nakajima, Susanne Schwenke, Stephan Lehr, Jürgen Heubach, Christoph Pohl, Joachim Reischl

Research output: Contribution to journalArticle

Abstract

Background: Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.Methods: Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists. The myxovirus protein A (MxA) induction assay, the cytopathic effect (CPE) assay (two laboratories), or the luciferase assay were used. Intra- and inter-laboratory agreement between assays with respect to NAb detection and NAb titer quantification were evaluated.Results: High agreement for NAb detection (kappa coefficient, 0.86) and for titer levels was observed for the intra-laboratory comparison in the laboratory using the MxA induction assay performed three years ago and now. A similarly high agreement for NAb detection (kappa coefficient, 0.87) and for titer quantification was noted for the MxA assay of this laboratory with one of two laboratories using the CPE assay. All other inter-laboratory comparisons showed kappa values between 0.57 and 0.68 and remarkable differences in individual titer levels.Conclusions: There are considerable differences in the detection and quantification of IFNB-induced NAbs among laboratories offering NAb testing for clinical practice using different assay methods. It is important that these differences are considered when interpreting NAb results for clinical decision-making and when developing general recommendations for potentially clinically meaningful NAb titer levels.

Original languageEnglish
Article number129
JournalJournal of Neuroinflammation
Volume9
DOIs
Publication statusPublished - Jun 15 2012

Fingerprint

Neutralizing Antibodies
Interferons
Interferon-beta
Staphylococcal Protein A
Orthomyxoviridae
Luciferases
Individuality
Multiple Sclerosis

Keywords

  • Clinical trials randomized controlled
  • IFNB-1b
  • Interferon beta
  • Multiple sclerosis
  • Neutralizing antibodies
  • Round robin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology
  • Neuroscience(all)

Cite this

Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies. / Hartung, Hans Peter; Kieseier, Bernd; Goodin, Douglas S.; Arnason, Barry G W; Comi, Giancarlo; Cook, Stuart; Filippi, Massimo; Jeffery, Douglas R.; Kappos, Ludwig; Bogumil, Timon; Stemper, Brigitte; Sandbrink, Rupert; Nakada, Yukiko; Nakajima, Haruhiko; Schwenke, Susanne; Lehr, Stephan; Heubach, Jürgen; Pohl, Christoph; Reischl, Joachim.

In: Journal of Neuroinflammation, Vol. 9, 129, 15.06.2012.

Research output: Contribution to journalArticle

Hartung, HP, Kieseier, B, Goodin, DS, Arnason, BGW, Comi, G, Cook, S, Filippi, M, Jeffery, DR, Kappos, L, Bogumil, T, Stemper, B, Sandbrink, R, Nakada, Y, Nakajima, H, Schwenke, S, Lehr, S, Heubach, J, Pohl, C & Reischl, J 2012, 'Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies', Journal of Neuroinflammation, vol. 9, 129. https://doi.org/10.1186/1742-2094-9-129
Hartung, Hans Peter ; Kieseier, Bernd ; Goodin, Douglas S. ; Arnason, Barry G W ; Comi, Giancarlo ; Cook, Stuart ; Filippi, Massimo ; Jeffery, Douglas R. ; Kappos, Ludwig ; Bogumil, Timon ; Stemper, Brigitte ; Sandbrink, Rupert ; Nakada, Yukiko ; Nakajima, Haruhiko ; Schwenke, Susanne ; Lehr, Stephan ; Heubach, Jürgen ; Pohl, Christoph ; Reischl, Joachim. / Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies. In: Journal of Neuroinflammation. 2012 ; Vol. 9.
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AU - Hartung, Hans Peter

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AU - Goodin, Douglas S.

AU - Arnason, Barry G W

AU - Comi, Giancarlo

AU - Cook, Stuart

AU - Filippi, Massimo

AU - Jeffery, Douglas R.

AU - Kappos, Ludwig

AU - Bogumil, Timon

AU - Stemper, Brigitte

AU - Sandbrink, Rupert

AU - Nakada, Yukiko

AU - Nakajima, Haruhiko

AU - Schwenke, Susanne

AU - Lehr, Stephan

AU - Heubach, Jürgen

AU - Pohl, Christoph

AU - Reischl, Joachim

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N2 - Background: Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.Methods: Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists. The myxovirus protein A (MxA) induction assay, the cytopathic effect (CPE) assay (two laboratories), or the luciferase assay were used. Intra- and inter-laboratory agreement between assays with respect to NAb detection and NAb titer quantification were evaluated.Results: High agreement for NAb detection (kappa coefficient, 0.86) and for titer levels was observed for the intra-laboratory comparison in the laboratory using the MxA induction assay performed three years ago and now. A similarly high agreement for NAb detection (kappa coefficient, 0.87) and for titer quantification was noted for the MxA assay of this laboratory with one of two laboratories using the CPE assay. All other inter-laboratory comparisons showed kappa values between 0.57 and 0.68 and remarkable differences in individual titer levels.Conclusions: There are considerable differences in the detection and quantification of IFNB-induced NAbs among laboratories offering NAb testing for clinical practice using different assay methods. It is important that these differences are considered when interpreting NAb results for clinical decision-making and when developing general recommendations for potentially clinically meaningful NAb titer levels.

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KW - Neutralizing antibodies

KW - Round robin

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