A sensitive radioimmunoprecipitation assay for assessing the clinical relevance of antibodies to IFN β
- 1Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
- 2Department of Neurology, University of British Columbia, Vancouver, BC, Canada
- 3Department of Clinical Neurology, Oxford, OX3 9DS, UK
- Correspondence to: Dr A Vincent, Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK; angela.vincent{at}imm.ox.ac.uk
- Received 13 January 2003
- Accepted 4 March 2003
- Revised 3 March 2003
Abstract
Background: Some multiple sclerosis (MS) patients treated with interferon beta (IFN β) develop antibodies to the drug. Neutralising antibody (NAB) assays for IFN β 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 β, and to correlate levels of antibodies with clinical response to IFN β treatment.
Methods: We established a radioimmunoprecipitation assay (RIPA) using 125I-IFN β. We tested NAB positive sera, healthy control sera, and serial samples of 33 IFN β-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 β-1a and -1b, and that there was a strong correlation between reactivity of NAB positive sera for 125I-IFN β-1b and for 125I-IFN β-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 β antibodies, and its use could help target expensive INF β treatments to those who will respond best.
- IFN β, interferon beta
- MS, multiple sclerosis
- MxA, myxovirus associated antigen
- NAB, neutralising antibody
- RIPA, radioimmunoprecipitation assay
Footnotes
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Competing interests: In addition to financial support for clinical and laboratory staff by way of research grants, JO, JP, and AV have variously received from Berlex Canada, Serono, Biogen, Schering, and Teva Marion reimbursements for attending conferences, speaker’s fees, fees for organising education, and consulting fees







