Anti-Interferon-γ Antibodies in a Patient Undergoing Interferon-γ Treatment for Systemic Mastocytosis

An 81-year-old woman with systemic mastocytosis responded to subcutaneous recombinant interferon-γ (rIFN-γ) treatment for about 6 months, when intestinal symptoms gradually recurred. A serum sample obtained 3 months later was positive for specific rIFN-γ-binding antibodies, which had been absent at the initiation of treatment. Cessation of IFN-γ therapy was followed by a slow decline of IFN antibody titers. The IFN-γ antibodies were of polyclonal or oligoclonal origin, with a predominance of IgG1 and IgG2 and small amounts of IgA and IgM. They neutralized the antiviral activity of both rIFN-γ and, less efficiently, natural IFN-γ in vitro. The time course of the neutralizing titers paralleled the IFN-binding activity of the antibodies. Thus, like other cytokines, rIFN-γ may be immunogenic in rare patients and elicit the formation of neutralizing antibodies that may impair the therapeutic activity of the drug and interfere with the endogenous IFN-γ system.