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

Clin Chim Acta 391(1-2):4 (2008) PMID 18249193

Introduction: Neutralizing antibodies (NAb) against interferon beta (IFN@b) reduce treatment efficacy in patients with multiple sclerosis (MS). Objective: We used the cross-reactivity of NAbs against IFN@b-1a or IFN@b-1b for improving the sensitivity of NAb measurement. Patients/methods: The study included sera from 185 MS patients treated at least 12 months (T1) with IFN@b-1a (Rebif(R); n=62 or Avonex(R); n=61) or IFN@b-1b (Betaferon(R); 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 IFN@b 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(R), Rebif(R) and Avonex(R), respectively. When IFN@b-1a (Rebif(R) or Avonex(R)) 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(R) and NAb-negative against IFN@b-1b. All the 33 NAb-positive patients at T1 were positive 3 to 6 months later. Conclusion: IFN@b-1a should be used for the NAb determination for an optimal evaluation of NAb-positive patients in MS patients treated with IFN@b.