Abstract
Background: Some multiple sclerosis (MS) patients treated with interferon beta (IFN ß) develop antibodies to the drug. Neutralising antibody (NAB) assays for IFN ß are expensive and the clinical relevance of the results has been debated.
Objective: To establish a cheap, sensitive, and reliable assay for antibodies to 125I-IFN ß, and to correlate levels of antibodies with clinical response to IFN ß treatment.
Methods: We established a radioimmunoprecipitation assay (RIPA) using 125I-IFN ß. We tested NAB positive sera, healthy control sera, and serial samples of 33 IFN ß-1b treated MS patients from the Vancouver cohort of the Berlex pivotal trial who had a high incidence of NABs.
Results: We found that the RIPA was highly sensitive for the detection of antibodies to IFN ß-1a and -1b, and that there was a strong correlation between reactivity of NAB positive sera for 125I-IFN ß-1b and for 125I-IFN ß-1a. The RIPA was more sensitive and consistent than the NAB. Moreover, there was a trend towards poorer MRI outcomes in RIPA positive patients, but not in NAB-positive patients.
Conclusions: The RIPA assay is sensitive and easy to perform. It should be of value in assessing the clinical impact of IFN ß antibodies, and its use could help target expensive INF ß treatments to those who will respond best.
Full Text
The Full Text of this article is available as a PDF (151.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Files J. G., Gray J. L., Do L. T., Foley W. P., Gabe J. D., Nestaas E., Pungor E., Jr A novel sensitive and selective bioassay for human type I interferons. J Interferon Cytokine Res. 1998 Dec;18(12):1019–1024. doi: 10.1089/jir.1998.18.1019. [DOI] [PubMed] [Google Scholar]
- Kivisäkk P., Alm G. V., Fredrikson S., Link H. Neutralizing and binding anti-interferon-beta (IFN-beta) antibodies. A comparison between IFN-beta-1a and IFN-beta-1b treatment in multiple sclerosis. Eur J Neurol. 2000 Jan;7(1):27–34. doi: 10.1046/j.1468-1331.2000.00002.x. [DOI] [PubMed] [Google Scholar]
- Palace J., Nairne A., Hyman N., Doherty T. V., Vincent A. A radioimmuno-precipitation assay for antibodies to botulinum A. Neurology. 1998 May;50(5):1463–1466. doi: 10.1212/wnl.50.5.1463. [DOI] [PubMed] [Google Scholar]
- Perini P., Facchinetti A., Bulian P., Massaro A. R., Pascalis D. D., Bertolotto A., Biasi G., Gallo P. Interferon-beta (INF-beta) antibodies in interferon-beta1a- and interferon-beta1b-treated multiple sclerosis patients. Prevalence, kinetics, cross-reactivity, and factors enhancing interferon-beta immunogenicity in vivo. Eur Cytokine Netw. 2001 Mar;12(1):56–61. [PubMed] [Google Scholar]
- Pungor E., Jr, Files J. G., Gabe J. D., Do L. T., Foley W. P., Gray J. L., Nelson J. W., Nestaas E., Taylor J. L., Grossberg S. E. A novel bioassay for the determination of neutralizing antibodies to IFN-beta1b. J Interferon Cytokine Res. 1998 Dec;18(12):1025–1030. doi: 10.1089/jir.1998.18.1025. [DOI] [PubMed] [Google Scholar]
- Rice G. P., Paszner B., Oger J., Lesaux J., Paty D., Ebers G. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-1b. Neurology. 1999 Apr 12;52(6):1277–1279. doi: 10.1212/wnl.52.6.1277. [DOI] [PubMed] [Google Scholar]
- Rudick R. A., Simonian N. A., Alam J. A., Campion M., Scaramucci J. O., Jones W., Coats M. E., Goodkin D. E., Weinstock-Guttman B., Herndon R. M. Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG) Neurology. 1998 May;50(5):1266–1272. doi: 10.1212/wnl.50.5.1266. [DOI] [PubMed] [Google Scholar]