Recombinant human a-interferon is now under intensive investigation as therapy for chronic Type B hepatitis. Recent reports have suggested that prolonged a- interferon therapy may induce autoimmune reactions. We have evaluated the problem of autoimmunity related to a-interferon therapy by testing for 15 different antibodies in the sera of 31 patients treated with a-interferon. No patient had autoantibodies before treatment; 27 (87%) of 31 patients developed at least one autoantibody. Eleven patients had antinuclear antibodies and 21 had smooth muscle antibodies, both of which usually developed during a-interferon therapy. In contrast, antibodies to endocrine organs such as thyroid microsomal, thyroglobulin and parietal cell antibodies arose in 12 patients, but usually several months after a-interferon treatment. The appearance of these autoantibodies did not correlate with disease activity or response to a- interferon. No patient developed autoantibodies specifically associated with autoimmune liver diseases such as liver kidney microsomal antibodies, autoantibodies to soluble liver antigen and the primary billiary cirrhosisspecific subtypes of antimitochondrial antibodies.
These results suggest that prolonged a-interferon therapy can induce autoantibody production and, in susceptible patients, may lead to autoimmune disorders.
a-Interferon (IFN-a) has been shown to be a promising therapeutic approach to the treatment of chronic Type B hepatitis (1, 2). Several large-scale, controlled trials of interferon therapy of this disease are presently under way. Interferons have many side effects, the most common of which are influenza-like symptoms (2). These side effects of interferon, however, are self-limited and largely restricted to the period of treatment; they disappear within weeks or months after stopping therapy. Recently, the development of autoantibodies has been reported to occur after interferon therapy (3, 4). The antibodies that appear are not those described in association with chronic active hepatitis (5-7). However, the possibility exists that interferon therapy of chronic T n e B hepatitis may induce autoimmune responses that may