This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Kivisäkk, P. Articles by Link, H. Search for Related Content PubMed PubMed Citation Articles by Kivisäkk, P. Articles by Link, H. Social Bookmarking                         What's this?

Neutralising and binding anti-interferon-β-1 b (IFN-b-1 b) antibodies during IFN-β-1 b treatment of multiple sclerosis

Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm

GV Alm

Department of Veterinary Immunology, Biomedical Centre, Uppsala, Sweden

WZ Tian

Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm

D. Matusevicius

Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm

S. Fredrikson

Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm

H. Link

Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm

Interferon-β-1b (IFN-β-1b) 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-β-1b 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-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I 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-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-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-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.

Key Words: multiple sclerosis • treatment • interferon-β • antibodies • B-cells

Multiple Sclerosis, Vol. 3, No. 3, 184-190 (1997)
DOI: 10.1177/135245859700300303


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?