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Perspectives on the neutralization of interferons by antibody

From the Department of Microbiology & Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI.

Address correspondence and reprint requests to Dr. Sidney E. Grossberg, Department of Microbiology & Molecular Genetics, 8701 Watertown Plank Road, Milwaukee, WI 53226; e-mail: segrossb{at}mcw.edu

Interferon (IFN) neutralizing antibody (NAb) interferes with the binding of the IFN molecule to its cellular receptor, thereby preventing receptor activation required to trigger the cascade of signal transduction events that lead to the varied actions of IFN. IFN antibody neutralization is measured in an IFN bioassay using cultured human cells. Antibody results need to be represented in a reproducibly quantitative manner to know what proportion of patients treated with an IFN preparation form NAbs and whether the levels of antibody measured are likely to have clinically adverse effects; however, antibody titers have been reported in various ways. Extensive experimental and theoretical analyses of IFN-antibody neutralization reactions have provided the basis for establishing a defined international unit of IFN NAb, described herein, so that the data from different laboratories can be readily compared and interpreted.