Variability in detection and quantification of interferon β-1b–induced neutralizing antibodies
1 Heinrich-Heine-Universität, Moorenstraße 5, Düsseldorf, 40225, Germany
2 University of California, Rm. M794, San Francisco, CA, 94143-0114, USA
3 Surgery Brain Research Institutes, 5812 S. Ellis Av., SBRI J209 (MC 2030), Chicago, IL, 60637, USA
4 Scientific Institute and University Hospital San Raffaele, Via Olgettina 60, Milan, 20132, Italy
5 UMD New Jersey Medical School, 65 Bergen Street - Suite 1435, Newark, NJ, 07101-1709, USA
6 The MS Center at Advance Neurology, Cornerstone Healthcare, 152 Kinderton Way, Suite 101, Advance, NC, 27006, USA
7 University Hospital, Petersgraben 4, Basel, CH-4031, Switzerland
8 Bayer HealthCare Pharmaceuticals, P.O. Box 1000, Montville, NJ, 07045-1000, USA
9 Bayer Pharma AG, Sellerstr 31, Berlin, 13342, Germany
10 Mitsubishi Chemical Medience Corporation, 3-30-1, Shimura, Itabashi-ku, Tokyo, 174-8555, Japan
11 University Hospital of Bonn, Sigmund-Freud-Str. 25, Bonn, 53127, Germany
12 Department of Neurology, Heinrich-Heine-Universität, Düsseldorf, D-40225, Germany
Journal of Neuroinflammation 2012, 9:129 doi:10.1186/1742-2094-9-129Published: 15 June 2012
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.
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.
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.
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.