Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies.
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.
Heinrich-Heine-Universität, Moorenstraße 5, Düsseldorf 40225, Germany. hans-peter.hartung@uni-duesseldorf.de
Hans-Peter
HP
Hartung
Bernd
B
Kieseier
Douglas S
DS
Goodin
Barry Gw
BG
Arnason
Giancarlo
G
Comi
Stuart
S
Cook
Massimo
M
Filippi
Douglas R
DR
Jeffery
Ludwig
L
Kappos
Timon
T
Bogumil
Brigitte
B
Stemper
Rupert
R
Sandbrink
Yukiko
Y
Nakada
Haruhiko
H
Nakajima
Susanne
S
Schwenke
Stephan
S
Lehr
Jürgen
J
Heubach
Christoph
C
Pohl
Joachim
J
Reischl
D000276:Adjuvants, Immunologic / Q000097:blood / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000097:blood*; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D015588:Observer Variation
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000068576:Interferon beta-1b; D016899:Interferon-beta