Antibodies to interferon-alpha: a novel type of autoantibody occurring after allogeneic bone marrow transplantation.

Antibodies to IFN-alpha have been recognized as a novel type of autoantibody developing after allogeneic BMT. Ninety-six patients undergoing BMT for various hematologic disorders were followed for the presence of spontaneous IFN-alpha antibodies until 12 years after transplantation. Seven of them (7.3%) developed IFN-alpha antibodies occurred late after BMT (> or = 15 months), rose to very high titers in some patients, and persisted for years despite combined immunosuppressive treatment. They were oligo- or polyclonal in nature, predominantly IgG with a broad IgG subclass distribution, and neutralized the antiviral and antiproliferative activity of various natural and recombinant IFN-alpha types including the patients' endogenous IFN-alpha in vitro. All antibody-positive recipients suffered from chronic GVHD (n = 5) or chronic viral hepatitis (n = 2), but the only significant association was with prior severe aplastic anemia (3/9, 33%; P = 0.022). There was no discernible HLA association of IFN antibody development. Although the clinical relevance of the IFN-alpha antibodies is uncertain they may interfere with cellular defence mechanisms and immune regulation after BMT.