Determination of interferon beta neutralizing antibodies in multiple sclerosis: improvement of clinical sensitivity of a cytopathic effect assay.

Journal: Clinica Chimica Acta; International Journal Of Clinical Chemistry
Published:
Abstract

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.

Authors
Catherine Massart, Jacqueline Gibassier, Jérôme De Seze, Marc Debouverie, Thibault Moreau, Jean Pelletier, Patrick Vermersch, Gilles Edan
Relevant Conditions

Multiple Sclerosis (MS)