Anti-IFN BAb and NAb antibodies

Interferon (IFN) -α, -β, and -γ have been used for the management of many diseases with varying clinical effects. Like many other proteins, all IFN species are potentially immunogenic, especially those produced by recombinant (r) gene technologies. The reported frequencies and titers of anti-IFN antibodies (Ab) vary considerably depending on diseases, IFN preparations and administration, and the types of assays being used.1–9⇓⇓⇓⇓⇓⇓⇓⇓ However, Ab-mediated decrease in bioactivity of IFN (ADB), a condition in which the clinical effect of continued injection of rIFN is minimized or abrogated, is increasingly being recognized.10 The need for clinically useful, inexpensive, and standardized screening assays is obvious, but attempts in this direction have failed despite the recommendation of the World Health Organization (WHO) to use biologic assays where antiviral neutralization is expressed as a titer defined as the reciprocal of the serum dilution that reduces the IFN potency from 10 LU/mL to 1 LU/mL (1 LU/mL is the level of IFN inducing 50% protection against the challenge virus in a given assay).11,12⇓ A major reason for the lack of standardization is the inconvenience and high cost of carrying out elaborate antiviral neutralization assays in the clinical setting; additionally, some of these assays have not been validated with regard to clinical relevance and therefore may provide little useful information to the clinician. Several years of use of such assays have contributed to the conception of, and distinction between, “non-neutralizing binding antibodies” (BAb) and “neutralizing antibodies” (NAb) occurring in patients receiving IFN therapies,13,14⇓ and this issue has been complicated further by the frequent use of BAb assays that may give false-positive results. Over the years, we have investigated naturally occurring and therapeutically induced antibodies to cytokines, including BAb and NAb to IFN preparations. …