Anticytokine antibodies in beta interferon-treated MS patients and the need for testing: Plight of the practicing neurologist

The recently reported decrease in beta interferon (IFNβ) efficacy induced by anti-IFNβ antibodies1 has prompted Berlex Laboratories (Richmond, CA), the maker of Betaseron, to offer to physicians and their patients testing for anti-IFNβ antibodies. Unfortunately the test being offered is an in-house, newly developed, unverified assay2 not available to other laboratories. The measurement of anti-IFNβ antibodies is not well established nor widely available, and neurologists are therefore caught in a very difficult situation. Those caring for MS patients on IFNβ need to know (for patients obviously not doing well on therapy) whether patients may be failing because the patient's antibody response to the drug has interfered with the bioavailability of the agent. Neurologists will find it difficult to obtain and interpret Berlex's new assay for their patients, but there is no alternative assay. An understanding of this complex problem requires some knowledge of (1) the biology of IFNβ, (2) antibody-binding antibody assays, and (3) the effects of antibodies on IFN bioavailability. Biology of IFNβ. Beta interferon is a member of the IFN family of cytokines. Alpha and gamma IFN are also in the IFN family. All three members have immunoregulatory, antiviral, antitumor, and cell growth regulatory functions. Two recombinant products available for MS, IFNβ-1b-Betaseron (Berlex) and IFNβ-1a-Avonex (Biogen), are structurally almost identical. Their amino acid sequences differ from each other by only one amino acid out of a total of 161, and IFNβ-1a is glycosylated at residue 80. The mechanism of action of IFNβ in MS is unknown. It seems most likely that the effect of IFNβ in MS is due to its immunomodulatory effects rather than to antiviral effects, although this has not been proved. In MS patients being treated with IFN, the molecule exerts its effects presumably by binding to receptors on target cells.3 The …