title: Measured neutralizing titers of IFN-beta neutralizing antibodies (NAbs) can depend on the preparations of IFN-beta used in the assay.
abstract: An immune response to recombinant human protein therapeutics, including type I interferons (IFNs), has the potential to have a serious negative impact on safety and efficacy. Monitoring of patients for neutralizing antibodies (NAbs) often is advisable. In the case of IFN-beta therapy for multiple sclerosis (MS), we obtained reproducible quantitative titers of NAbs using an improved and well-characterized assay based on a 10-fold reduction of a challenge dose of IFN-beta. However, the observed titer was significantly affected by the preparation of IFN-beta used as the assay challenge. NAb titers obtained using IFN-beta1b averaged 3-5-fold lower than titers of the same sample assayed using either IFN-beta1a or human fibroblast-derived IFN-beta. This was the case whether neutralizing serum was obtained from patients on therapy with IFN-beta1a or IFN-beta1b. The reason for this apparent titer difference is not fully understood but appears to be related to protein folding or other structural properties that differentiate the IFN-beta1b both from commercial IFN-beta1a preparations and from human fibroblast-derived IFN-beta.
authors.affiliation: J. Files Consulting, 120 C Street, San Rafael, CA 94901, USA. jimfiles@comcast.net
authors.forename: James G
authors.initials: JG
authors.lastname: Files
authors.forename: David
authors.initials: D
authors.lastname: Hargrove
authors.forename: Lourdes
authors.initials: L
authors.lastname: Delute
authors.forename: Marc
authors.initials: M
authors.lastname: Cantillon
mesh_terms: D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007106:Immune Sera / Q000096:biosynthesis / Q000097:blood*; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology*; D007518:Isoantibodies / Q000096:biosynthesis / Q000097:blood*; D064547:Myxovirus Resistance Proteins; D009500:Neutralization Tests; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured