Neutralizing antibodies, to interferon

Hartung HP, Munschauer F, Schellekens H. Significance of neutralizing antibodies to interferon beta during treatment of multiple sclerosis expert opinions based on the Proceedings of an International Consensus Conference. Eur J Neurol 2005 12 588-601. 

Deisenhammer F, Schellekens H, Bertolotto A. Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis. J Neurol. 2004 251(suppl 2) II31—1139. 

Both binding and neutralizing antibodies to interferon alfa can be detected in interferon alfa-treated patients, and the incidence or clinical significance of these antibodies is the subject of continuous controversy, which has been addressed in a number of studies or general reviews (SED-13, 1096) (SEDA-20, 330) (SEDA-21, 373) (156,323-325). 

Antonelli G, Current M, Turriziani O, Dianzani F. Neutralizing antibodies to interferon-alpha relative frequency in patients treated with different interferon preparations. J Infect Dis 1991 163(4) 882-5. 

In multiple sclerosis, neutralizing antibodies to recombinant interferon beta occurred in 12-38% of patients treated for 2-3 years (3-5,70). There were no adverse consequences in patients who developed antibodies to interferon beta-la (4), but there was reduced therapeutic efficacy in terms of clinical relapse rate or magnetic resonance imaging in several patients who had neutralizing antibodies to interferon beta-lb (SEDA-20, 332) (5,71). 

Khan OA, Dhib-Jalbut SS. Neutralizing antibodies to interferon beta-la and interferon beta-lb in MS patients are cross-reactive. Neurology 1998 51(6) 1698-702. 

Bertolotto A. Neutralizing antibodies to interferon beta Implications for the management of multiple sclerosis. Curr Opin Neurol 2004 17 241-246. 

Giovannoni, G., Munschauer, F.E., and Deisenhammer, F. (2002) Neutralizing antibodies to interferon beta during the treatment of multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, 73, 465 469. 

Sorensen PS. Effects of neutralizing antibodies to interferon beta in multiple sclerosis a... 

Immunogenicity Nine percent of patients treated with peginterferon alfa-2a with or without ribavirin tablets developed binding antibodies to interferon alfa-2a, as assessed by an ELISA assay. The clinical and pathological significance of the appearance of serum neutralizing antibodies is unknown. 

Immunogenicity Approximately 2% of patients receiving peginterferon alfa-2b or interferon alfa-2b with or without ribavirin capsules developed low-titer (160 or less) neutralizing antibodies to peginterferon alfa-2b or interferon alfa-2b. 

Pastore G. Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. Liver 1993 13(3) 146-50. 

McKay F, Schibeci S, Heard R et al (2006) Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple sclerosis patients a comparison of three methods in a large Australasian cohort. J Immunol Methods 310 20-29... 

Neutralizing Antibodies Antibodies to beta interferons can form over time and reduce the clinical effect of beta interferons.40 The clinical effect of neutralizing antibodies is seen 18 to... 

The problem of the immunogenic nature of many human recombinant DNA proteins, and the potential to generate antibodies to a normal human protein, is of special interest to the immunotoxicologist. For example, 3 of 16 patients administered the rDNA-derived interferon-a (clone A) developed antibodies of the IgG class that were undetectable prior to or during therapy (Gutterman et al., 1982). These antibodies were capable of in vitro neutralization of interferon activity, although in vivo neutralization of interferon has not been documented. Since there are several different subtypes of interferon-a s, some contain epitopes not present on their own interferon subtype. Similarly, two patients treated with interferon-/ for many months developed high-titered antibody, which in one case was correlated with an inability of the patient s fibroblasts to produce interferon (Vallbracht et al., 1982). 

Cross AH, Antel IP. Antibodies to beta-interferons in multiple sclerosis can we neutralize the controversy Neurology 1998 50(5) 1206-8. 

If a patient taking interferon decompensates and has neutralizing antibodies in the blood, most practitioners will stop the medication. In this situation it is controversial whether to rechallenge the patient at a later date with interferon therapy. Many clinicians will only rechallenge with interferon therapy if the patient does not do well on other therapies. 

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