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Clinical relevance of NAb assays? |
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| In any bioassay for neutralisation of exogenously added IFN it is important to realize whether the amount of added IFN is relevant to the clinical situation in which the test is being used. For example, the dose-response curves of our antiviral neutralisation assay show a plateau of maximum protection at IFN levels between 2.5 and 3 LU/ml (1). With the recommended use of 10 LU/ml of IFN, 2/3 might be neutralised by NAb without being noticed, and with the use of 5% serum this would correspond to a blood neutralising capacity of up to 150 LU/ml of IFN. This is about 30 times the peak blood levels obtained during high dose IFN-beta1a therapy (2). With addition of even larger amounts of IFN, up to 100 LU/ml have been used, the reported frequencies of NAb-positives may become very low. Thus, patients testing negative for NAb in a low sensitivity assay may have substantial amounts of circulating NAb and therefore be at risk of developing Ab-mediated decrease in bioactivity of IFN (ADB) with continued IFN therapy.
On the other hand, patients positive only in an extremely sensitive antiviral neutralisation assay may not exhibit measurable ADB. We believe, however, that the appearance of even small amounts of NAb, for example in IFN-beta-treated MS patients, may provide essential information by allowing the clinician to change therapy or institute measures to prevent further NAb production in time to prevent irreversible CNS damage. Cited references: 1. Ross C, Clemmesen KM, Svenson M, Sorensen PS, Koch-Henriksen N, Skovgaard GL, Bendtzen K. Immunogenicity of interferon-b in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group. Ann Neurology 2000;48:706-12. 2. Munafo A, Trinchard-Lugan II, Nguyen TX, Buraglio M. Comparative pharmacokinetics and pharmacodynamics of recombinant human interferon beta-1a after intramuscular and subcutaneous administration. Eur J Neurol 1998;5:187-93. KB 2003 |
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