title: Neutralising and binding anti-interferon-beta-I b (IFN-beta-I b) antibodies during IFN-beta-I b treatment of multiple sclerosis.
abstract: Interferon-beta-I b (IFN-beta-I b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-beta-I b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-beta-I b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-beta-I b antibodies, presently not believed to impede the clinical efficacy of IFN-beta-I b, were demonstrated by an immunoassay in some patients after 1 month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-beta-I a and natural IFN-beta were also found in a majority of IFN-beta-I b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-beta-I b for 1-23 months had elevated numbers of anti-IFN-beta-I b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-beta-I b is immunogenic in MS patients. High levels of anti-IFN-beta-I b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-beta-I b antibodies might also occur spontaneously.
authors.affiliation: Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Kivisäkk
authors.forename: G V
authors.initials: GV
authors.lastname: Alm
authors.forename: W Z
authors.initials: WZ
authors.lastname: Tian
authors.forename: D
authors.initials: D
authors.lastname: Matusevicius
authors.forename: S
authors.initials: S
authors.lastname: Fredrikson
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology; D001681:Biological Assay; D001773:Blood Cells / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D009500:Neutralization Tests
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a