Determination of interferon beta neutralizing antibodies in multiple sclerosis: improvement of clinical sensitivity of a cytopathic effect assay.
BACKGROUND
Neutralizing antibodies (NAb) against interferon beta (IFNbeta) reduce treatment efficacy in patients with multiple sclerosis (MS).


OBJECTIVE
We used the cross-reactivity of NAbs against IFNbeta-1a or IFNbeta-1b for improving the sensitivity of NAb measurement.


METHODS
The study included sera from 185 MS patients treated at least 12 months (T1) with IFNbeta-1a (Rebif; n=62 or Avonex; n=61) or IFNbeta-1b (Betaferon; n=62). NAbs were measured by CPE in all the sera using the WISH cell line infected by the bovine stomatitis vesicular virus. NAb titres were expressed in ten-fold reduction (TRU)/mL. NAb-positive titres at T1 were also measured 3 to 6 months later (T2).


RESULTS
At T1, with the classical CPE assay using the IFNbeta type (1a or 1b) according to the molecule administered, 29/180 (15.7%) patients had positive NAb titres: 9/62 (14.5%), 14/62 (22.6%) and 6/61 (9.8%) subjects were treated with Betaferon, Rebif and Avonex, respectively. When IFNbeta-1a (Rebif or Avonex) was used, NAb-positive results were found in 33/185 (17.8%) patients. They included the 29 patients previously found positive with the classical CPE method and 7 other subjects treated with Betaferon and NAb-negative against IFNbeta-1b. All the 33 NAb-positive patients at T1 were positive 3 to 6 months later.


CONCLUSIONS
IFNbeta-1a should be used for the NAb determination for an optimal evaluation of NAb-positive patients in MS patients treated with IFNbeta.
Massart
Catherine
C
Unité d'Hormonologie, CHU Rennes, France. catherine.massart@chu-rennes.fr
Gibassier
Jacqueline
J
de Seze
Jérôme
J
Debouverie
Marc
M
Moreau
Thibault
T
Pelletier
Jean
J
Vermersch
Patrick
P
Edan
Gilles
G
D000328:Adult; D000906:Antibodies / Q000009:adverse effects* / Q000276:immunology; D001681:Biological Assay / Q000379:methods*; D003588:Cytopathogenic Effect, Viral; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D009500:Neutralization Tests; D012680:Sensitivity and Specificity; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000906:Antibodies; D016899:Interferon-beta; D000068556:Interferon beta-1a