Abstract
While autoantibodies (autoAbs) to IFN-beta are rarely found in humans, antibodies (Abs) to IFN-beta are frequently seen in patients receiving prolonged therapies with recombinant human IFN-beta. As autoAbs, they neutralize wild-type IFN-beta, they cross-react with both currently used IFNbeta biopharmaceuticals, but not IFN-alpha, and they interfere with biological and immunometric assays for IFN-beta in vitro and in vivo. Although anti- IFN-beta Abs usually neutralize IFN-beta in vivo, making further therapies useless, there is experimental support for the idea that some anti-IFN-beta Abs, at least early during ‘immunization‘, may function as enhancers and paradoxically prolong and amplify the activities of IFN-beta in vivo. There are significant difficulties in obtaining reliable methods for monitoring patients on prolonged IFN-beta therapies. These include IFN-beta analyses in blood required for optimal and individualized therapies, and Ab detection induced during therapy. In an effort to assess the clinical relevance of in vitro Ab measurements, many investigators distinguish between ‘binding’ Abs (BAbs) and in vitro ‘neutralizing’ Abs (NAbs) even though such a distinction may not be justified in real terms. For example, the so-called non-neutralizing BAbs may affect drug bioavailability and drug clearance, while NAbs may not necessarily neutralize circulating IFN-beta in vivo. Moreover, anti-IFN-beta Abs may cause serious complications and theoretically initiate autoimmune reactions whether or not they neutralize in vivo. Regular screening for NAbs and discontinuation of therapy in multiple sclerosis patients with sustained high-level NAbs are now generally recommended.
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References
Ann Marrie, R. and Rudick, R. A. 2006. Drug Insight: interferon treatment in multiple sclerosis. Nat. Clin. Pract. Neurol. 2:34–44.
Bendtzen, K. 2003. Anti-IFN BAb and NAb antibodies: A minireview. Neurology 61(Suppl. 5):S6–S10.
Borg, F. A. and Isenberg, D. A. 2007. Syndromes and complications of interferon therapy. Curr. Opin. Rheumatol. 19:61–66.
Brickelmaier, M., Hochman, P. S., Baciu, R., Chao, B., Cuervo, J. H., and Whitty, A. 1999. ELISA methods for the analysis of antibody responses induced in multiple sclerosis patients treated with recombinant interferon-beta. J. Immunol. Methods 227:121–135.
Gilli, F., Marnetto, F., Caldano, M., Sala, A., Malucchi, S., Capobianco, M., and Bertolotto, A. 2006. Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1. Mult. Scler. 12:47–57.
Grossberg, S. E. 2003. Perspectives on the neutralization of interferons by antibody. Neurology 61:S21–S23.
Hermeling, S., Jiskoot, W., Crommelin, D., Bornaes, C., and Schellekens, H. 2005. Development of a transgenic mouse model immune tolerant for human interferon beta. Pharm. Res. 22:847–851.
Kawade, Y. 1980. An analysis of neutralization reaction of interferon by antibody: a proposal on the expression of neutralization titer. J. Interferon Res. 1:61–70.
Pachner, A. R. 2003. Anti-IFNb antibodies in IFNb-treated MS patients. Neurology 61(Suppl. 5):S1–S5.
Pachner, A. R., Dail, D., Pak, E., and Narayan, K. 2005. The importance of measuring IFNbeta bioactivity: monitoring in MS patients and the effect of anti-IFNbeta antibodies. J. Neuroimmunol. 166:180–188.
Ross, C., Clemmesen, K. M., Svenson, M., Sorensen, P. S., Koch-Henriksen, N., Skovgaard, G. L., and Bendtzen, K. 2000. Immunogenicity of interferon-b in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group. Ann. Neurol. 48:706–712.
Ross, C., Svenson, M., Clemmesen, K. M., Sorensen, P. S., Koch-Henriksen, N., and Bendtzen, K. 2006. Measuring and evaluating interferon-beta-induced antibodies in patients with multiple sclerosis. Mult. Scler. 12:39–46.
Schellekens, H. 2002. Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin. Ther. 24:1720–1740.
Selmi, C., Lleo, A., Zuin, M., Podda, M., Rossaro, L., and Gershwin, M. E. 2006. Interferon alpha and its contribution to autoimmunity. Curr. Opin. Investig. Drugs 7:451–456.
Thorpe, R. and Swanson, S. J. 2005. Current methods for detecting antibodies against erythropoietin and other recombinant proteins. Clin. Diagn. Lab. Immunol. 12:28–39.
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© 2008 American Association of Pharmaceutical Scientists
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Bendtzen, K., Kromminga, A. (2008). Case Study: Immunogenicity of Interferon-Beta. In: Weert, M.v., Møller, E.H. (eds) Immunogenicity of Biopharmaceuticals. Biotechnology: Pharmaceutical Aspects, vol VIII. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75841-1_7
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DOI: https://doi.org/10.1007/978-0-387-75841-1_7
Publisher Name: Springer, New York, NY
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