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

Abstract

IntroductionNeutralizing antibodies (NAb) against interferon beta (IFNβ) reduce treatment efficacy in patients with multiple sclerosis (MS). ObjectiveWe used the cross-reactivity of NAbs against IFNβ-1a or IFNβ-1b for improving the sensitivity of NAb measurement. Patients/methodsThe study included sera from 185 MS patients treated at least 12 months (T1) with IFNβ-1a (Rebif®; n=62 or Avonex®; n=61) or IFNβ-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). ResultsAt T1, with the classical CPE assay using the IFNβ 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 IFNβ-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 IFNβ-1b. All the 33 NAb-positive patients at T1 were positive 3 to 6 months later. ConclusionIFNβ-1a should be used for the NAb determination for an optimal evaluation of NAb-positive patients in MS patients treated with IFNβ.