title: Further study on the specificity and incidence of neutralizing antibodies to interferon (IFN) in relapsing remitting multiple sclerosis patients treated with IFN beta-1a or IFN beta-1b.
abstract: The development of neutralizing antibodies (NAbs) to interferon (IFN) is a common phenomenon of IFN beta therapy for relapsing-remitting multiple sclerosis (RRMS) patients. Here we examine the specificity of NAbs developed during therapy for RRMS with recombinant interferon (rIFN) beta-1a or rIFN beta-1b, and study the effect of switching from rIFN beta-1a to rIFN beta-1b on the incidence and specificity of NAbs. The relative ability to neutralize rIFN beta-1a and beta-1b was assayed in sera positive for NAbs derived from RRMS patients treated with either rIFN beta-1a (N=9) or rIFN beta-1b (N=16), while the incidence and specificity of NAbs to IFN beta developed during therapy were studied in 50 RRMS patients who were treated for two years with rIFN beta-1a followed by a further year either switching to rIFN beta-1b (N=34) or continuing treatment with rIFN beta-1a (N=16). The results show that all positive sera, independent of the source, may recognize both forms of rIFN beta and that a further year of treatment does not significantly affect the incidence and specificity of the NAbs developed during the first two years of treatment even if treatment is switched to a different type of IFN beta. The data then suggests that it is unlikely that the administration of rIFN beta-1b to anti-rIFN beta-1a NAbs-positive patients can overcome the inhibitory effect exerted by the serum antibodies (and vice versa), and that a further period of treatment with IFN beta-1b in patients previously treated with rIFN beta-1a does not significantly change the pattern of antibody response to IFN beta.
authors.affiliation: Department of Biomedicine, University of Pisa, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
authors.forename: E
authors.initials: E
authors.lastname: Simeoni
authors.forename: F
authors.initials: F
authors.lastname: Bagnato
authors.forename: C
authors.initials: C
authors.lastname: Pozzilli
authors.forename: O
authors.initials: O
authors.lastname: Turriziani
authors.forename: R
authors.initials: R
authors.lastname: Tesoro
authors.forename: P
authors.initials: P
authors.lastname: Di Marco
authors.forename: C
authors.initials: C
authors.lastname: Gasperini
authors.forename: C
authors.initials: C
authors.lastname: Fieschi
authors.forename: F
authors.initials: F
authors.lastname: Dianzani
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D001667:Binding, Competitive; D018592:Cross-Over Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012075:Remission, Spontaneous; D012189:Retrospective Studies
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a